AU2014240289B2

AU2014240289B2 - Fused diimidazodiazepine compounds and methods of use and manufacture thereof

Info

Publication number: AU2014240289B2
Application number: AU2014240289A
Authority: AU
Inventors: Ramachandra S. Hosmane; Raj Kumar; Venu Raman
Original assignee: Johns Hopkins University
Current assignee: Johns Hopkins University
Priority date: 2008-09-23
Filing date: 2014-10-03
Publication date: 2015-12-03
Anticipated expiration: 2029-09-23
Also published as: AU2014240289A1

Abstract

Abstract The invention encompasses novel compounds and pharmaceutically acceptable salts thereof and compositions including therapeutically or prophylactically effective amounts of such compounds or pharmaceutically acceptable salts thereof. The invention also encompasses methods for treating or preventing diseases and disorders associated abnormal cell growth, for example, treating or preventing cancer or tumor growth, which methods include administering to a mammal in need thereof a composition comprising a therapeutically or prophylactically effective amount of a compound of the invention or a pharmaceutically acceptance salt thereof. CC) toC C (C f- C6 *c)- -Co L(-.> coJ W co cO I- O -o -o -o -:; -o C~ r o 03 r C- > C=> j C 16 I C' C COj aSuc -CN 043 C _. -C0 -: Cco cz~ C Ls C C% L 4=(5 C) L LL- 3 -C oo C: Co r LU i i Z Co= LU r L I I co a-c CD ~ D CD U C) Q? CO C 2 C a L:) = 4 N--. 0 C oL OT7FnlrTrTT~rrTl ITTTT'rF 1" TY T -1

Description

EDITORIAL NOTE 2014240289 - There are 115 pages of Description - The 1 st page is not numbered FUSED DIIMIDAZODIAZEPINE COMPOUNDS AND METHODS OF USE AND MANUFACTURE THEREOF [0011 This application claims the benefit of U.S. provisional patent application number 61/099,324, filed September 23, 2008, which is incorporated herein by reference. 1. FIELD OF THE INVENTION 10021 The invention encompasses novel compounds and pharmaceutically acceptable salts thereof and compositions including therapeutically or prophylactically effective amounts of such compounds or pharmaceutically acceptable salts thereof. The invention also encompasses methods for treating or preventing diseases and disorders associated abnormal cell growth, for example, treating or preventing cancer or tumor growth, which methods include administering to a mammal in need thereof a composition comprising a therapeutically or prophylactically effective amount of a compound of the invention or a pharmaceutically acceptable salt thereof 2. BACKGROUND OF THE INVENTION (003J Treatment of cancer varies based on the type of cancer and its stage. The stage of a cancer refers to how much it has grown and whether the tumor has spread from its original location. If the cancer is confined to one location and has not spread, the most common goals for treatment are surgery and cure. This is often the case with skin cancers, as well as cancers of the lung, breast, and colon. [004] If the tumor has spread to local lymph nodes only, sometimes these can also be removed. If surgery cannot remove all of the cancer, the options for treatment include radiation, chemotherapy, or both. Some cancers require a combination of surgery, radiation, and chemotherapy. 10051 Although current radiotherapeutic agents, chemotherapeutic agents and biological toxins are potent cytotoxins, they do not discriminate between normal and malignant cells, producing adverse effects and dose-limiting toxicities. There remains a need for lung cancer specific cancer markers.

[006] The present inventors have identified novel compounds that are effective in discriminately inhibiting the growth &f cancer and tumor cells while allowing healthy "normal" cells to remain unaffected. [007] Surprisingly, the methods and compositions of the invention fulfill the needs and satisfy other objects and advantages that will become apparent from the description which follows 3. SUMMARY OF THE INVENTION [008] The invention encompasses compounds and compositions and methods comprising the compounds of Formulas I-V that are useful for treating or preventing a disease or disorder including, but not limited to, conditions caused by uncontrolled cell growth, hyperproliferation of cells, tumor growth, and cancers. [009] The invention also encompasses methods for treating or preventing lung cancer, pancreatic cancer, leukemia, breast cancer, liver cancer, kidney cancer, ovarian cancer, human glioblastoma and prostate cancer, which comprises administering to a mammal in need of such treatment or prevention a therapeutically or prophylactically effective amount of a composition comprising a compound of Formula I-V, or a pharmaceutically acceptable salt or prodrug thereof, and a pharmaceutically acceptable vehicle. [0101 In certain embodiments, a composition or formulation comprising a compound of Formula I-V is useful in treating or preventing conditions caused by uncontrolled cell growth. 1011] In certain embodiments, a composition or formulation comprising a compound of Formula I-V is useful in killing abnormal or cancerous cells while simultaneously not affecting healthy or normal cells. [0121 In certain embodiments, a composition or formulation comprising a compound of Formula I-V act as cytotoxic agents. [013] In certain embodiments, a composition or formulation comprising a compound of Formula I-V act as apoptotic agents. [0141 As described herein, the compositions that are useful in the methods of the invention encompass compounds of Formulas I-V. [015] In one embodiment, the invention encompasses compositions and formulations for treating or preventing diseases or disorders comprising a compound of Formula (I): 2 r(R 9(b) N NN 7 N N (I) or pharmaceutically acceptable salts and prodrugs thereof, wherein: R, R', and R are each independently a hydrogen, hydroxyl; substituted or unsubstituted: cyclic and acyclic alkyl group, cyclic and acyclic alkenyl group, cyclic and acyclic alkynyl group, aryl group, alkylaryl group, arylalkyl group, benzyl group, cyclic and acyclic heteroalkyl group, heteroaryl group; -C(O)R 3 ; -C(S)R 3 ; -S(O)R 3 ; -S(Q) 2

R

3 ; -C(O)NR 4

R

5 ;

-C(S)NR

3

R

4 ; -C(X)YRR 6 ; -p-D-ribosyl; -a-D-ribosyl; -0-L-ribosyl; -a-L-ribosyl; 2' deoxy-p-D-ribosyl; 2'-deoxy-f-L-ribosyl; 2'-deoxy-a-D-ribosyl; 2'-deoxy-a-L-ribosyl; and ribose or deoxyribose sugars substituted with one or more halogens; R, R', and R" can also form a ring with one or more C, S, 0, N atoms such that, for example, R and R' together include: R7 (Z)n

R

7 is a hydrogen; hydroxyl; substituted and unsubstuted: cyclic and acyclic alkyl group, group, alkenyl group, alkynyl group, aryl group, aryloxy group, alkylary group, aryalkyl group, heteroaryl group, heterocycloalkyl group; -C(O)alkyl; -C(O)alkenyl; -C(O)alkynyl; -C(O)aryl; -C(O)benzyl; -C(O)NR 3

R

4 ; -C(S)alkyl; -C(S)alkenyl; -C(S)alkynyl; -C(S)aryl; -C(S)benzyl; -C(S)NR 3

R

4 ; -C(X)YR'R 2 ; wherein Q is 0, NH, or S; 3 X is 0, N, or S; Y is O, CH 2 , NH, or S; Z is CH, N, P, or C; ----- is a single bond or double bond; wherein if --- is a double bond, R 2 or R 7 is independently 0, S, or NH; n is 1, 2, 3, or 4; and r, r', and r" are each independently an integer from I to about 3. 10161 In certain illustrative embodiments, R, R', and R are each independently are a substituted benzyl, alkyl, aryl, cycloalkyl, heteroaryl, or heterocycloalkyl with one ore more substituents, such as, but not limited to, -H, -F, -Cl, -Br, -1, -OH, azido, -SH, alkyl, aryl, heteroalky, alkyoxyl, alkylthiol, amino, hydroxylamino, N-alkylamino, -NN-dialkylanino, -NN-dimethylamino, acyl, alkyloxycarbonyl, sulfonyl, urea, -NO 2 , triazolyl. [0171 In another embodiment, the invention encompasses compositions and formulations for treating or preventing diseases or disorders comprising a compound of Formula (II): R OR2 R3 R 4 N _N R5. (II) or pharmaceutically acceptable salts and prodrugs thereof, wherein R', R2, R3, R4, and R5 are each independently a hydrogen; hydroxyl; substituted or unsubstituted: cyclic and acyclic alkyl group, cyclic and acyclic alkenyl group, cyclic and acyclic alkynyl group, aryl group, alkylaryl group, arylalkyl group, benzyl group, cyclic and acyclic heteroalkyl group, heteroaryl group; -C(O)R 3 ; -C(S)R 3 ; -S(O)R3; -S(O)2R3; 4

-C(O)NR

4

R

5 ; -C(S)NR 3

R

4 ; -C(X)YRR 6 ; -p-D-ribosyl; -a-D-ribosyl; -p-L-ribosyl; -a-L ribosyl; 2'-deoxy-p-D-ribosyl; 2'-deoxy-p-L-ribosyl; 2'-deoxy-cc-D-ribosyl; 2'-deoxy-a L-ribosyl; and ribose or deoxyribose sugars substituted with one or more halogens; R' and R3 or R2 and R4 can also form a ring with one or more C, S, 0, N atoms such that R' and R3 or R 2 and R4 together include R7 (Z)~ R7 is a hydrogen; hydroxyl; substituted and unsubstuted: cyclic and acyclic alkyl group, group, alkenyl group, alkynyl group, aryl group, aryloxy group, alkylary group, aryalkyl group, heteroaryl group, heterocycloalkyl group; -C(O)alkyl; -C(O)alkenyl; -C(O)alkynyl; C(O)aryl; -C(O)benzyl; -C(O)NR 3

R

4 ; -C(S)alkyl; -C(S)alkenyl; -C(S)alkynyl; -C(S)aryl; -C(S)benzyl; -C(S)NR 3

R

4 ; -C(X)YR'R 2 ; wherein X is 0, N, or S; Y is 0, CH2, NH, or S; Z is CH, N, P, or C; ----- is a single bond or double bond; wherein if ----- is a double bond, R2 or R7 is independently 0, S, or NH; and n is 1, 2, 3, or 4. 10181 In certain illustrative embodiments, R', R2, R, R 4 , and R 5 are each independently are a substituted benzyl, alkyl, aryl, cycloalkyl, heteroaryl, or heterocycloalkyl with one ore more substituents, such as, but not limited to, -H, -F, -Cl, -Br, -I, -OH, azido, -SH, alkyl, aryl, heteroalky, alkyoxyl, alkylthiol, amino, hydroxylamino, N-alkylamino, -N,N-dialkylamino, N,N-dimethylamino, acyl, alkyloxycarbonyl, sulfonyl, urea, -NO 2 , triazolyl. 1019] In another embodiment, the invention encompasses compositions and formulations for treating or preventing diseases or disorders comprising a compound of Formula (III): 5 R N O R3 N N 4 N N R5 (III) or pharmaceutically acceptable salts and prodrugs thereof, wherein R', R, R4, and R 5 are each independently a hydrogen; hydroxyl; substituted or unsubstituted: cyclic and acyclic alkyl group, cyclic and acyclic alkenyl group, cyclic and acyclic alkynyl group, aryl group, alkylaryl group, arylalkyl group, benzyl group, cyclic and acyclic heteroalkyl group, heteroaryl group; -C(O)R 3 ; -C(S)R 3 ; -S(O)R 3 ; -S(O) 2

R

3 ;

-C(O)NR

4 R; -C(S)NR 3

R

4 ; -C(X)YRR 6 ; -p-D-ribosyl; -a-D-ribosyl; -p-L-ribosyl; -a-L ribosyl; 2'-deoxy-p-D-ribosyl; 2'-deoxy-p-L-ribosyl; 2'-deoxy-az-D-ribosyl; 2'-deoxy-a L-ribosyl; and ribose or deoxyribose sugars substituted with one or more halogens; R' and R3 can also form a ring with one or more C, S, 0, N atoms such that R' and R 3 together include R7 (Z),

R

4 ; -C(S)alkyl; -C(S)alkenyl; -C(S)alkynyl; -C(S)aryl; -C(S)benzyl; -C(S)NR 3

R

4 ; -C(X)YR'R 2 ; wherein X is 0, N, or S; 6 Y is 0, CH 2 , NH, or S; Z is CH, N, P, or C; ----- is a single bond or double bond; wherein if ---- is a double bond, R 2 or R7 is independently 0, S, or NH; and n is 1, 2, 3, or 4. [020] In certain illustrative embodiments, R', R, R 4 , and R' are not all hydrogen. [021J In certain illustrative embodiments, R', R, R4, and R 5 are each independently are a substituted benzyl, alkyl, aryl, cycloalkyl, heteroaryl, or heterocycloalkyl with one ore more substituents, such as, but not limited to, -H, -F, -Cl, -Br, -I, -OH, azido, -SH, alkyl, aryl, heteroalky, alkyoxyl, alkylthiol, amino, hydroxylamino, N-alkylamino, -N,N-dialkylamino, N,N-dimethylamino, acyl, alkyloxycarbonyl, sulfonyl, urea, -NO 2 , triazolyl. [022] In another embodiment, the invention encompasses compositions and formulations for treating or preventing diseases or disorders comprising a compound of Formula (IV): 0 N N N N R R N N (IV) or pharmaceutically acceptable salts and prodrugs thereof, wherein R3 and R are each independently a hydrogen; hydroxyl; substituted or unsubstituted: cyclic and acyclic alkyl group, cyclic and acyclic alkenyl group, cyclic and acyclic alkynyl group, aryl group, alkylaryl group, arylalkyl group, benzyl group, cyclic and acyclic heteroalkyl group, heteroaryl group; -C(O)R 3 ; -C(S)R 3 ; -S(O)R 3 ; -S(O) 2

R

3 ; -C(O)NR 4 R;

-C(S)NR

3

R

4 ; -C(X)YRR 6 ; -p-D-ribosyl; -a-D-ribosyl; -p-L-ribosyl; -a-L-ribosyl; 2' deoxy-0-D-ribosyl; 2'-deoxy-p-L-ribosyl; 2'-deoxy-a-D-ribosyl; 2'-deoxy-t-L-ribosyl; and ribose or deoxyribose sugars substituted with one or more halogens. [0231 In certain illustrative embodiments, R 3 and R 4 are both not hydrogen. 7 10241 In certain illustrative embodiments, R 3 and R 4 are each independently are a substituted benzyl, alkyl, aryl, cycloalkyl, heteroaryl, or heterocycloalkyl with one ore more substituents, such as, but not limited to, -H, -F, -Cl, -Br, -1, -OH, azido, -SH, alkyl, aryl, heteroalky, alkyoxyl, alkylthiol, amino, hydroxylamino, N-alkylamino, -N,N-dialkylamino, -N,N-dimethylamino, acyl, alkyloxycarbonyl, sulfonyl, urea, -NO 2 , triazolyl. [0251 In another embodiment, the invention encompasses compositions and formulations for treating or preventing diseases or disorders comprising a compound of Formula (V): N F 5 H0 C N R OH

,

/N N N N (V) or pharmaceutically acceptable salts and prodrugs thereof, wherein R3, R4, and R5 are each independently a hydrogen; hydroxyl; substituted or unsubstituted: cyclic and acyclic alkyl group, cyclic and acyclic alkenyl group, cyclic and acyclic alkynyl group, aryl group, alkylaryl group, arylalkyl group, benzyl group, cyclic and acyclic heteroalkyl group, heteroaryl group; -C(O)R 3 ; -C(S)R 3 ; -S(O)R3; -S(0)2R; -C(O)NR4R 5 ;

-C(S)NR

3

R

4 ; -C(X)YRR 6 ; -p-D-ribosyl; -a-D-ribosyl; -p-L-ribosyl; -a-L-ribosyl; 2' deoxy-p-D-ribosyl; 2'-deoxy-p-L-ribosyl; 2'-deoxy-a-D-ribosyl; 2'-deoxy-ca-L-ribosyl; and ribose or deoxyribose sugars substituted with one or more halogens. 10261 In certain illustrative embodiments, R3, R4, and R5 are not each hydrogen. 10271 In certain illustrative embodiments, R3, R4, and R5 are each independently are a substituted benzyl, alkyl, aryl, cycloalkyl, heteroaryl, or heterocycloalkyl with one ore more substituents, such as, but not limited to, -H, -F, -Cl, -Br, -I, -OH, azido, -SH, alkyl, aryl, heteroalky, alkyoxyl, alkylthiol, amino, hydroxylamino, N-alkylamino, -N,N-dialkylamino, N,N-dimethylamino, acyl, alkyloxycarbonyl, sulfonyl, urea, -NO 2 , triazolyl. [028] In various other illustrative embodiments of the invention, the compounds of the invention can be encompassed by the following illustrative embodiments. 8 [029] The present invention may be understood more fully by reference to the figures, detailed description, and examples, which are intended to exemplify non-limiting embodiments of the invention. 4. BRIEF DESCRIPTION OF THE DRAWINGS [030] Figure 1 illustrates 'H NMR (S, DMSO-d 6 , J in Hz in parentheses) data of illustrative compounds 3 and 11-14a. [031] Figure 2 illustrates "C NMR (6, DMSO-d 6 ) data of illustrative compounds 3 and 11-14. 1032] Figure 3 illustrates a three-Bond 'H-C3 Coupling (HMBC) in illustrative compounds 3 and 11-14. [033] Figure 4 illustrates 1H NMR (8, DMSO-d, J in Hz in parentheses) data of compound 5. [034] Figure 5 illustrates 'IH NMR (6, DMSO-d 6 , J in Hz in parentheses) data of compound 6. [035] Figure 6 illustrates "C NMR (6, DMSO-d 6 ) data of compound 6. [036] Figure 7 illustrates 'H NMR (6, DMSO-d 6 , J in Hz in parentheses) data of compound 7. 10371 Figure 8 illustrates "C NMR (6, DMSO-d 6 ) data of compound 7. [038] Figure 9 illustrates 'H NMR (6, DMSO-d 6 , J in Hz in parentheses) data of illustrative compound 9. [039] Figure 10 illustrates ' 3 C NMR (5, DMSO-d 6 ) data of illustrative compound 9. [040] Figure 11 illustrates 'H NMR (6, DMSO-d 5 , J in Hz in parentheses) data of illustrative compound 3. [041] Figure 12 illustrates '3C NMR (8, DMSO-d) data of illustrative compound 3. [042] Figure 13 illustrates "C NMR DEPT 135 (6, DMSO-d 6 ) data of illustrative compound 3. [043] Figure -14 illustrates HMQC NMR (6, DMSO-d 6 ) data of illustrative compound 3. [044] Figure 15 illustrates HMBC NMR (6, DMSO-d 6 ) data of illustrative compound 3. [045] Figure 16 illustrates 'H NMR (6, DMSO-d 6 , J in Hz in parentheses) data of illustrative compound 11. [046J Figure 17 illustrates "C NMR (6, DMSO-d) data of illustrative compound 11. [0471 Figure 18 illustrates "C NMR DEPT 135 (6, DMSO-4) data of illustrative compound 11. [048] Figure 19 illustrates HMQC NMR (6, DMSO-d 6 ) data of illustrative compound 11. [049] Figure 20 illustrates HMBC NMR (6, DMSO-d) data of illustrative compound 11. 9 10501 Figure 21 illustrates 'H NMR (6, DMSO-d 6 , J in Hz in parentheses) data of illustrative compound 12. 10511 Figure 22 illustrates 13 C NMR (6, DMSO-d 6 ) data of illustrative compound 12. 10521 Figure 23 illustrates ' 3 C NMR DEPT 135 (6, DMSO-d 6 ) data of illustrative compound 12. [053] Figure 24 illustrates HMQC NMR (6, DMSO-d) data of illustrative compound 12. [054] Figure 25 illustrates HMBC NMR (6, DMSO-d 6 ) data of illustrative compound 12. [055] Figure 26 illustrates 'H NMR (6, DMSO-d, J in Hz in parentheses) data of illustrative compound 13. [056] Figure 27 illustrates ' 3 C NMR (6, DMSO-d) data of illustrative compound 13. [057] Figure 28 illustrates "C NMR DEPT 135 (6, DMSO-d 6 ) data of illustrative compound 13. [0581 Figure 29 illustrates HMQC NMR (6, DMSO-d 6 ) data of illustrative compound 13. [059] Figure 30 illustrates HMBC NMR (6, DMSO-d) data of illustrative compound 13. [060] Figure 31 illustrates 'H NMR (6, DMSO-d, J in Hz in parentheses) data of illustrative compound 14. 10611 Figure 32 illustrates 13 C NMR (6, DMSO-d 6 ) data of illustrative compound 14. [062] Figure 33 illustrates ' 3 C NMR DEPT 135 (S, DMSO-d 6 ) data of illustrative compound 14. [0631 Figure 34 illustrates HMQC NMR (6, DMSO-d 6 ) data of illustrative compound 14. [064] Figure 35 illustrates HMBC NMR (6, DMSO-d 6 ) data of illustrative compound 14. [065] Figure 36 illustrates normal lung cell lines when contacted with illustrative compound of the invention compound 3. 10661 Figure 37 illustrates lung cancer cell lines when contacted with illustrative compound of the invention compound 3. [067] Figure 38 illustrates glioblastoma human cell lines when contacted with illustrative compound of the invention compound 3. [068] Figure 39 illustrates prostate cancer cell lines when contacted with illustrative compound of the invention compound 3. 1069J Figure 40 illustrates immunoblast analyses for DDX-3 expression in lung, prostate, and glioblastoma cell lines. 10 [0701 Figure 41: Top panel: A) QRT-PCR of DDX3 levels in a series of immortalized normal breast cell lines (1-2) and breast cancer cell lines (3-7). The breast cancer cell lines are in the order of aggressive phenotype. Top panel: B) Immunoblot analysis for DDX3 expression in the identical cell lines as above. Bottom panel: A) QRT-PCR of DDX3 levels in different grades of human breast carcinoma samples. Bottom panel: B) Immunostaining for DDX3 levels in normal human breast sections and in breast carcinoma sample. [071] Figure 42: A) Tumor growth rate in the mammary fat pad of SCID mice (preclinical breast cancer model) using wild type and DDX3 knockdown MDA-MB-231 cells. B) Cross section of lungs of animals injected orthotopically (mammary fat pad) with MDA-MB-231 and MDAMB-23 I-shDDX3 cells. Note that the lungs from MDA-MB-23 1-shDDX3 injected animals showed no tumor formation as compared to the wild type cells (black arrows points to lung metastasis). [0721 Figure 43: MTS assays of MCF I OA cells (immortalized normal breast cell line) incubated with Compound 3 drug. X-axis indicates concentration of drug used. The cells were incubated for three days (fresh drug was added daily) following which cell viability was determined. [0731 Figure 44: MTS assays of MCF IOA cells (immortalized normal breast cell line) incubated with Compound 3 drug. X-axis indicates concentration of drug used. The cells were incubated for three days (fresh drug was added daily) following which cell viability was determined. [074] Figure 45: MTS assays of MCF-7 cells (breast cancer cell line) incubated with Compound 3 drug. X-axis indicates concentration of drug used, The cells were incubated for three days (fresh drug was added daily) following which cell viability was determined. [075] Figure 46: MTS assays of MDA-MB-468 cells (breast cancer cell line) incubated with Compound 3 drug. X-axis indicates concentration of drug used. The cells were incubated for three days (fresh drug was added daily) following, which cell viability was determined. [076J Figure 47: MTS assays of MDA-MB-231 cells (breast cancer cell line) incubated with Compound 3 drug. X-axis indicates concentration of drug used. The cells were incubated for three days (fresh drug was added daily) following which cell viability was determined. [077] Figure 48: MTS assays of HL60T cells (leukemia cell line) incubated with Compound 3 drug. X-axis indicates concentration of drug used. The cells were incubated for three days (fresh drug was added daily) following which cell viability was determined. 11 [078] Figure 49: MTS assays of HNT34 cells (leukemia cell line) incubated with Compound 3 drug. X-axis indicates concentration of drug used. The cells were incubated for three days (fresh drug was added daily) following which cell viability was determined. [079] Figure 50: MTS assays of KG101 cells (leukemia cell line) incubated with Compound 3 drug. X-axis indicates concentration of drug used. The cells were incubated for three days (fresh drug was added daily) following which cell viability was determined. 10801 Figures 51-54 illustrate Toxicity studies of Compound 3 in SCID mouse. Data shown is that of 500 pM of RK-33 drugs that were injected twice daily for four weeks. Following that the drug was injected once a week for three weeks. At the end of the experiment the animals were sacrificed and histopathology performed. The range of drug dose tested was from 500 to 100 pM. 5. DETAILED DESCRIPTION OF THE INVENTION 5.1. DEFINITIONS 10811 As used herein and unless otherwise indicated, the term "alkoxy group" means an -0 alkyl group, wherein alkyl is as defined herein. An alkoxy group can be unsubstituted or substituted with one or two suitable substituents. Preferably, the alkyl chain of an alkyloxy group is from 1 to 6 carbon atoms in length, referred to herein, for example, as "(Ci-CIo)alkoxy." [082] As used herein and unless otherwise indicated, the term "alkenyl group" means a monovalent unbranched or branched hydrocarbon chain having one or more double bonds therein. The double bond of an alkenyl group can be unconjugated or conjugated to another unsaturated group. Suitable alkenyl groups include, but are not limited to (C 2 -Cg)alkenyl groups, such as vinyl, allyl, butenyl, pentenyl, hexenyl, butadienyl, pentadienyl, hexadienyl, 2 ethylhexenyl, 2-propyl-2-butenyl, 4-(2-methyl-3-butene)-pentenyl. An alkenyl group can be unsubstituted or substituted with one or two suitable substituents. 1083] As used herein and unless otherwise indicated, the term "alkylalkoxy" or "alkyloxyalkyl group" means a saturated, monovalent unbranched or branched hydrocarbon chain covalently bonded to an oxygen and covalently bonded to a second a saturated, monovalent unbranched or branched hydrocarbon chain (e.g., -alkyl-0-alkyl). [0841 As used herein and unless otherwise indicated, the term "alkyl" or "alkyl group" means a substituted or unsubstituted, saturated, monovalent unbranched or branched hydrocarbon chain. Examples of alkyl groups include, but are not limited to, (CI-Ci o)alkyl groups, such as methyl, ethyl, propyl, isopropyl, 2-methyl-I -propyl, 2-methyl-2-propyl, 2-methyl-1 -butyl, 3-methyl-1 12 butyl, 2-methyl-3-butyl, 2,2-dimethyl-1-propyl, 2-methyl-I-pentyl, 3-methyl-i-pentyl, 4-methyl I -pentyl, 2-methyl-2-pentyl, 3-methyl-2-pentyl, 4-methyl-2-pentyl, 2,2-dimethyl-l -butyl, 3,3 dimethyl-l-butyl, 2-ethyl-1-butyl, butyl, isobutyl, t-butyl, pentyl, isopentyl, neopentyl, and hexyl, and longer alkyl groups, such as heptyl, and octyl. An alkyl group can be unsubstituted or substituted with one or two suitable substituents. [085] As used herein and unless otherwise indicated, the term "alkynyl group" means monovalent unbranched or branched hydrocarbon chain having one or more triple bonds therein. The triple bond of an alkynyl group can be unconjugated or conjugated- to another unsaturated group. Suitable alkynyl groups include, but are not limited to, (C2-C6)alkynyl groups, such as ethynyl, propynyl, butynyl, pentynyl, hexynyl, methylpropynyl, 4-methyl-I -butynyl, 4-propyl-2 peritynyl, and 4-butyl-2-hexynyl. An alkynyl group can be unsubstituted or substituted with one or two suitable substituents. (086J As used herein and unless otherwise indicated, the term "aryl group" means a monocyclic or polycyclic-aromatic radical comprising carbon and hydrogen atoms. Examples of suitable aryl groups include, but are not limited to, phenyl, tolyl, anthacenyl, fluorenyl, indenyl, azulenyl, and naphthyl, as well as benzo-fused carbocyclic moieties such as 5,6,7,8-tetrahydronaphthyl. An aryl group can be unsubstituted or substituted with one or two suitable substituents. Preferably, the aryl group is a monocyclic ring, wherein the ring comprises 6 carbon atoms, referred to herein as "(C 6 )aryl." [0871 As used herein and unless otherwise indicated, the term "aryloxy group" means an -0 aryl group, wherein aryl is as defined herein. An aryloxy group can be unsubstituted or substituted with one or two suitable substituents. Preferably, the aryl ring of an aryloxy group is a monocyclic ring, wherein the ring comprises 6 carbon atoms, referred to herein as

"(C

6 )aryloxy." [0881 As used herein, the term "benzyl" means -CH 2 -phenyl. [089] As used herein, the term "carbonyl" group is a divalent group of the fonnula -C(O)-. [090] As used herein and unless otherwise indicated, the term "compounds of the invention" means, collectively, the compounds of formulas I, II, III, IV, and V and pharmaceutically acceptable salts thereof as well as compounds depicted herein including Compounds 3, 11, 12, 13, 14, 21, 23, 25, 27, and 101-193. The compounds of the invention are identified herein by their chemical structure and/or chemical name. Where a compound is referred to by both a 13 chemical structure and a chemical name, and that chemical structure and chemical name conflict, the chemical structure is detenrninative of the compound's identity. The compounds of the invention may contain one or more chiral centers and/or double bonds and, therefore, exist as stereoisomers, such as double-bond isomers (i.e., geometric isomers), enantiomers, or diastereomers. According to the invention, the chemical structures depicted herein, and therefore the compounds of the invention, encompass all of the corresponding compound's enantiomers and stereoisomers, that is, both the stereomerically pure form (e.g., geometrically pure, enantiomerically pure, or diastereomerically pure) and enantiomeric and stereoisomeric mixtures. Enantiomeric and stereoisomeric mixtures can be resolved into their component enantiomers or stereoisomers by well known methods, such as chiral-phase gas chromatography, chiral-phase high performance liquid chromatography, crystallizing the compound as a chiral salt complex, or crystallizing the compound in a chiral solvent. Enantiomers and stereoisomers can also be obtained from stereomerically- or enantiomerically-pure intermediates, reagents, and catalysts by well known asymmetric synthetic methods. [0911 As used herein and unless otherwise indicated, the term cyclicc alkyl" and "cycloalkyl group" are used synonymously and each means a monocyclic or polycyclic saturated ring comprising carbon and hydrogen atoms and having no carbon-carbon multiple bonds. Examples of cycloalkyl groups include, but are not limited to, (C 3

-C

7 )cycloalkyl groups, such as cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, and cycloheptyl, and saturated cyclic and bicyclic terpenes. A cycloalkyl group can be unsubstituted or substituted by one or two suitable substituents. Preferably, the cycloalkyl group is a monocyclic ring or bicyclic ring. 10921 As used herein and unless otherwise indicated, the term "halogen" means fluorine, chlorine, bromine, or iodine. Correspondingly, the meaning of the terms "halo" and "Hal" encompass fluoro, chloro, bromo, and iodo. [093] As used-herein and unless otherwise indicated, the term "formulation" refers to a composition comprising a compound of the invention that is described in a particular dosage form (e.g, tablet) or with a particular dosage amount (e.g., 30 mg/kg). [094J As used herein and unless otherwise indicated, the term "heteroaryl group" means a monocyclic- or polycyclic aromatic ring comprising carbon atoms, hydrogen atoms, and one or more heteroatoms, preferably 1 to 3 heteroatoms, independently selected from nitrogen, oxygen, and sulfir. Illustrative examples of heteroaryl groups include, but are not limited to, pyridinyl, pyridazinyl, pyrimidyl, pyrazyl, triazinyl, pyrrolyl, pyrazolyl, imidazolyl, (1,2,3,)- and (1,2,4) 14 triazolyl, pyrazinyl, pyrimidinyl, tetrazolyl, firyl, thienyl, isoxazolyl, thiazolyl, firyl, phienyl, isoxazolyl, and oxazolyl. A heteroaryl group can be unsubstituted or substituted with one or two suitable substituents. Preferably, a heteroaryl group is a monocyclic ring, wherein the ring comprises 2 to 5 carbon atoms and I to 3 heteroatoms, referred to herein as "(C-CS)heteroaryl." [095] As used herein and unless otherwise indicated, the term "heterocycloalkyl group" means a monocyclic or polycyclic ring comprising carbon and hydrogen atoms and at least one heteroatom, preferably, I to 3 heteroatoms selected from nitrogen, oxygen, and sulfur, and having no unsaturation. Examples of heterocycloalkyl groups include pyrrolidinyl, pyrrolidino, piperidinyl, piperidino, piperazinyl, piperazino, morpholinyl, morpholino, thiomorpholinyl, thiomorpholino, and pyranyl. A heterocycloalkyl group can be unsubstituted or substituted with one or two suitable substituents. Preferably, the heterocycloalkyl group is a monocyclic or bicyclic ring, more preferably, a monocyclic ring, wherein the ring comprises from 3 to 7 carbon atoms and form 1 to 3 heteroatoms, referred to herein as (CrC7)heterocycloalkyl. [096] As used herein and unless otherwise indicated, the term "heterocyclic radical" or "heterocyclic ring" means a heterocycloalkyl group or a heteroaryl group. [0971 As used herein and unless otherwise indicated, the term "hydrocarbyl group" means a monovalent group selected from (C-Cs)alkyl, (C 2 -Cs)alkenyl, and (C2-Cs)alkynyl, optionally substituted with one or two suitable substituents. Preferably, the hydrocarbon chain of a hydrocarbyl group is from I to 6 carbon atoms in length, referred to herein as "(C C6)hydrocarbyl." 10981 When administered to a mammal (e.g., to an animal for veterinary use or to a human for clinical use), the compounds of the invention can be optionally administered in isolated form. As used herein, "isolated" means that the compounds of the invention are separated from other components of either (a) a natural source, such as a plant or ceH, preferably bacterial culture, or (b) a synthetic organic chemical reaction mixture, preferably, via conventional techniques, the compounds of the invention are purified. As used herein, "purified" means that when isolated, the isolate contains at least 80% preferably at least 90%, more preferably at least 95%, and most preferably at least 99% of a compound of the invention by weight of the isolate. [0991 The phrase "pharmaceutically acceptable salt(s)," as used herein includes but is not limited to salts of acidic or basic groups that may be present in compounds used in the present compositions. Compounds included in the present compositions that are basic in nature are capable of forming a wide variety of salts with various inorganic and organic acids. The acids 15 that may be used to prepare pharmaceutically acceptable acid addition salts of such basic compounds are those that form non-toxic acid addition salts, i.e., salts containing pharmacologically acceptable anions including, but not limited to, sulfuric, citric, maleic, acetic, oxalic, hydrochloride, hydrobromide, hydroiodide, nitrate, sulfate, bisulfate, phosphate, acid phosphate, isonicotinate, acetate, lactate, salicylate, citrate, acid citrate, tartrate, oleate, tannate, pantothenate, bitartrate, ascorbate, succinate, maleate, gentisinate, fumarate, gluconate, glucaronate, saccharate, fonnate, benzoate, glutamate, methanesulfonate, ethanesulfonate, benzenesulfonate, p-toluenesulfonate and pamoate (Le., 1,1 '-methylene-bis-(2-hydroxy-3 naphthoate)) salts. Compounds included in the present compositions that include an amino moiety may form pharmaceutically acceptable salts with various amino acids, in addition to ihe acids mentioned above. Compounds, included in the present compositions, that are acidic in nature are capable of forming base salts with various pharmacologically acceptable cations. Examples of such salts include alkali metal or alkaline earth metal salts and, particularly, calcium, magnesium, sodium lithium, zinc, potassium, and iron salts. [01001 As used herein and unless otherwise indicated, the term "pharmaceutically acceptable prodrug" means a derivative of a compound that can hydrolyze, oxidize, or otherwise react under biological conditions (in vitro or in vivo) to provide the compound. Examples of prodrugs include, but are not limited to, compounds that comprise biohydrolyzable moieties such as biohydrolyzable amides, biohydrolyzable esters, biohydrolyzable carbamates, biohydrolyzable carbonates, biohydrolyzable ureides, and biohydrolyzable' phosphate analogues. Other examples of prodrugs include compounds that comprise oligonucleotides, peptides, lipids, aliphatic and aromatic groups, or NO, NO 2 , ONO, and ONO2 moieties. Prodrugs can typically be prepared using well known methods, such as those described in Burger's Medicinal Chemistry and Drug Discovery, pp. 172, 178, 949, 982 (Manfred E. Wolff ed., 5th ed. 1995), and Design of Prodrugs (H. Bundgaard ed., Elselvier, New York 1985). [01011 As used herein and unless otherwise indicated, the terms "biohydrolyzable amide," "biohydrolyzable ester," "biohydrolyzable carbamate," "biohydrolyzable carbonate," "biohydrolyzable ureide," "biohydrolyzable phosphate" mean an amide, ester, carbamate, carbonate, ureide, or phosphate, respectively, of a compound that either: 1) does not interfere with the biological activity of the compound but can confer upon that compound advantageous properties in vivo, such as uptake, duration of action, or onset of action; or 2) is biologically inactive but is converted in vivo to the biologically active compound. Examples of 16 biohydrolyzable esters include, but are not limited to, lower alkyl esters, lower acyloxyalkyl esters (such as acetoxylmethyl, acetoxyethyl, aminocarbonyloxy-methyl, pivaloyloxymethyl, and pivaloyloxyethyl esters), lactonyl esters (such as phthalidyl and thiophthalidyl esters), lower alkoxyacyloxyalkyl esters (such as methoxycarbonyloxy-methyl, ethoxycarbonyloxy-ethyl and isopropoxycarbonyloxyethyl esters), alkoxyalkyl esters, choline esters, and acylamino alkyl esters (such as acetamidomethyl esters). Examples of biohydrolyzable aides include, but are not limited to, lower alkyl amides, a amino acid amides, alkoxyacyl aides, and alkylaminoalkyl-carbonyl amides. Examples of biohydrolyzable carbamates include, but are not limited to, lower alkylamines, substituted ethylenediamines, aminoacids, hydroxyalkylamines, heterocyclic and heteroaromatic amines, and polyether amines. [0102] As used herein and unless otherwise indicated, the term "phenyl" means -CSH 5 . A phenyl group can be unsubstituted or substituted with one or two suitable substituents. [01031 As used herein and unless otherwise indicated, the terms "substituted" and "a suitable substituent" means a group that does not nullify the synthetic or pharmaceutical utility of the compounds of the invention or the intermediates useful for preparing them. Examples of substituted groups or suitable substituents include, but are not limited to: (C-Cs)alkyl; (C Cs)alkenyl; (C 1 -Cs)alkynyl; (C6)aryl; (C3-CS)heteroaryl; (C 3

-C

7 )cycloalkyl; (CrC 3 )alkoxy; (Cs)aryloxy; -CN; -OH; SH, oxo; halo, -NO 2 , -CO 2 H; -NH 2 ; -NHOH, -NH((CI-Cs)alkyl); N((C-C)alkyl) 2 ; -NH((C 6 )aryl); -NHO((C -Cs)alkyl); -N(O(C 1 -Cs)alkyl) 2 ; -NH(O(C 6 )aryl); S((C 1 -Cs)alkyl); -S((C,-Cs)alkyl) 2 ; -S((C 6 )aryl); (=0); C(S), -N((C 6 )aryl) 2 ; -CHO; -C(O)((Cr Cg)alkyl); -C(O)((C 6 )aryl); -CO2((C-C)alkyl); and -CO2((C 6 )aryl), -C(S)((C-Cs)alkyl); C(S)((C 6 )aryl); -SO2((CrCg)alkyl); -SO2((C6)aryl), and -SO3H, -C(S)O((C-Cs)alkyl); C(S)(O)((C 6 )aryl). In certain illustrative embodiments, the substituents can be one or more than one suitable groups, such as, but not limited to, -F, -Cl, -Br, -I, -OH, azido, -SH, alkyl, aryl, heteroalky, alkyoxyl, alkylthiol, amino, hydroxylamino, N-alkylamino, -N;N-dialkylamino, N,N-dimethylamino, acyl, alkyloxycarbonyl, sulfonyl, urea, -NO 2 , triazolyl. One of skill in art can readily choose a suitable substituent based on the stability and pharmacological and synthetic activity of the compound of the invention. [0104] As used herein and unless otherwise indicated, the phrase "therapeutically effective amount" of a composition of the invention is measured by the therapeutic effectiveness of a compound of the invention, wherein at least one adverse effect of a disorder is ameliorated or alleviated. 17 10105] The terms "treating or preventing" are intended to include preventing, eradicating, or inhibiting the resulting increase of undesired physiological activity associated with a disorder, for example, in the context of the therapeutic or prophylactic methods of the invention. In another embodiment, the term treating or preventing includes antagonistic effects, e.g., diminishment of the activity or production of mediators of a disorder. 5.2 Compounds of the Invention [0106] As set forth herein, the invention includes, but is not limited to, compounds, compositions and formulations for treating or preventing treating or preventing a disease or disorder including, but not limited to, conditions caused by uncontrolled cell growth, hyperproliferation of cells, tumor growth, and cancers, for example, lung cancer, pancreatic cancer, leukemia, breast cancer, liver cancer, kidney cancer, ovarian cancer, human glioblastoma and prostate cancer, which comprises administering to a mammal in need of such treatment or prevention a therapeutically or prophylactically effective amount of a composition comprising a compound of Formula I-, or a pharmaceutically acceptable salt or prodrug thereof, and a pharmaceutically acceptable vehicle. In certain embodiments, a composition or formulation comprising a compound of Formula I-V is useful in treating or preventing conditions caused by uncontrolled cell growth.In certain embodiments, a composition or formulation comprising a compound of Formula I-V is useful in killing abnormal or cancerous cells while simultaneously not affecting healthy or normal cells.In certain embodiments, a composition or formulation comprising a compound of Formula I-V act as cytotoxic agents.In certain embodiments, a composition or formulation comprising a compound of Formula I-V act as apoptotic agents. [0107] The invention encompasses methods of treating or preventing diseases and disorders described herein by administering a composition or formulation comprising a compound of Formulas I-V or a pharmaceutically acceptable salt or prodrug thereof. [01081 As described herein, the compositions that are useful in the methods of the invention encompass compounds of Formulas I-V. [0109J In one embodiment, the invention encompasses compounds and compositions and formulations for treating or preventing diseases or disorders comprising a compound of Formula (I): 18 r(R 9 9(b) 'N Na 7 3 N N (I) or pharmaceutically acceptable salts and prodrugs thereof, wherein: R, R', and R" are each independently a hydrogen, hydroxyl; substituted or unsubstituted: cyclic and acyclic alkyl group, cyclic and acyclic alkenyl group, cyclic and acyclic alkynyl group, aryl group, alkylaryl group, arylalkyl group, benzyl group, cyclic and acyclic heteroalkyl group, heteroaryl group; -C(O)R 3 ; -C(S)R 3 ; -S(O)R 3 ; -S(O) 2

R

3 ; -C(O)NR 4

R

5 ;

-C(S)NR

3

R

4 ; -C(X)YR'R 6 ; -p-D-ribosyl; -a-D-ribosyl; -- L-ribosyl; -a-L-ribosyl; 2' deoxy-p-D-ribosyl; 2'-deoxy-p-L-ribosyl; 2'-deoxy-a-D-ribosyl; 2'-deoxy-a-L-ribosyl; and ribose or deoxyribose sugars substituted with one or more halogens; R, R', and R can also form a ring with one or more C, S, 0, N atoms such that, for example, R and R' together in-clude: R7 (Z)n R7 is a hydrogen; hydroxyl; substituted and unsubstuted: cyclic and acyclic alkyl group, group, alkenyl group, alkynyl group, aryl group, aryloxy group, alkylary group, aryalkyl group, heteroaryl group, heterocycloalkyl group; -C(O)alkyl; -C(O)alkenyl; -C(O)alkyny; -C(O)aryl; -C(O)benzyi; -C(O)NR 3

R

4 ; -C(S)alkyl; -C(S)alkenyl; -C(S)alkynyl; -C(S)aryl; -C(S)benzyl; -C(S)NR 3

R

4 ; -C(X)YR'R 2 ; wherein Q is 0, NH, or S; 19 X is 0, N, or S; Y is 0, CH 2 , NH, or S; Z is CH, N, P, or C; -- is a single bond or double bond; wherein if --- is a double bond, R2 or R 7 is independently 0, S, or NH; n is 1, 2, 3, or 4; and r, r', and r" are each independently an integer from 1 to about 3. [01101 In certain illustrative embodiments, R, R', and R"are each independently are a substituted benzyl, alkyl, aryl, cycloalkyl, heteroaryl, or heterocycloalkyl with one ore more substituents, such as, but not limited to, -H, -F, -Cl, -Br, -1, -OH, azido, -SH, alkyl, aryl, heteroalky, alkyoxyl, alkylthiol, amino, hydroxylanino, N-alkylamino, -NN-dialkylamino, -NN-dimethylamino, acyl, alkyloxycarbonyl, sulfonyl, urea, -NO 2 , triazolyl. 101111 In certain illustrative embodiments, the compounds of the invention do not include compounds where both R, R', and R" are all hydrogen. [0112] In certain illustrative embodiments, the substituents can be one or more than one suitable groups, such as, but not limited to, -F, -Cl, -Br, -I, -OH, azido, -SH, alkyl, aryl, heteroalky, alkyoxyl, alkylthiol, amino, hydroxylamino, N-alkylamino, -NN-dialkylamino, -N,N dimethylamino, acyl, alkyloxycarbonyl, sulfonyl, urea, -NO 2 , triazolyl. [0113J In one embodiment, R is hydrogen. In another embodiment, R is an alkyl group: In another embodiment, R is an alkoxy group. In another embodiment, R is an alkylalkoxy group. In another embodiment, R is an alkenyl group. In another embodiment, R is alkynyl group. In another embodiment, R is an aryl group. In another embodiment, R is aryloxy group. In another embodiment, R is benzyl group. In another embodiment, R is heteroaryl group. In another embodiment, R is heterocycloalkyl group. In another embodiment, R is a cycloalkyl group. In another embodiment, R is a benzyl group. 10114] In certain illustrative embodiments. R is a benzyl group substituted with one or more -F groups. 101151 In certain illustrative embodiments, R is a benzyl group substituted with one or more -Cl groups. 101161 In certain illustrative embodiments, R is a benzyl group substituted with one or more -Br groups. 20 10117J In certain illustrative embodiments, R is a benzyl group substituted with one or more -I groups. 10118] In certain illustrative embodiments, R is a benzyl group substituted with one or more OH groups. [01191 In certain illustrative embodiments, R is a benzyl group substituted with one or more azido groups. [01201 In certain illustrative embodiments, R is a benzyl group substituted with one or more -SH groups. 10121] In certain illustrative embodiments, R is a benzyl group substituted with one or more alkyl. [01221 In certain illustrative embodiments, R is a benzyl group substituted with one or more aryl groups. [0123] In certain illustrative embodiments, R is a benzyl group substituted with one or more heteroalkyl groups. [0124] In certain illustrative embodiments, R is a benzyl group substituted with one or more' alkyloxyl groups. [0125J In.certain illustrative embodiments, R is a benzyl group substituted with one or more alkylthiol groups. [0126] In certain illustrative embodiments, R is a benzyl group substituted with one or more amino groups. [01271 In certain illustrative embodiments, R is a benzyl group substituted with one or more hydroxylamino groups. [0128] In certain illustrative embodiments, R is a benzyl group substituted with one or more N alkylamino groups. 101291 In certain illustrative embodiments, R is a benzyl group substituted with one or more N,N-dialkylamino groups. [0130] In certain illustrative embodiments, R is a benzyl group substituted with one or more N,N-dimethylamino groups. [0131] In certain illustrative embodiments, R is a benzyl group substituted with one or more acyl groups. [01321 In certain illustrative embodiments, R is a benzyl group substituted with one or more alkyloxycarbonyl groups. groups 21 [01331 In certain illustrative embodiments, R is a benzyl group substituted with one or more sulfonyl groups. 101341 In certain illustrative embodiments, R is a benzyl group substituted with one or more urea groups. [0135] In certain illustrative embodiments, R is a benzyl group substituted with one or more NO 2 groups. 101361 In certain illustrative embodiments, R is a benzyl group substituted with one or more triazolyl groups. 10137] In one embodiment, R' is hydrogen. In another embodiment, R' is an alkyl group. In another embodiment, R' is an alkoxy group. In another embodiment, R' is an alkylalkoxy group. In another embodiment, R' is an alkenyl group. In another embodiment, R' is alkynyl group. In another embodiment, R' is an aryl group. In another embodiment, R' is aryloxy group. In another embodiment, R' is benzyl group. In another embodiment, R' is heteroaryl group. In another embodiment, R' is heterocycloalkyl group. In another embodiment, R' is a cycloalkyl group. In another embodiment, R' is a benzyl group. 101381 In certain illustrative embodiments, R' is a benzyl group substituted with one or more -F groups. [0139] In certain illustrative embodiments, R' is a benzyl group substituted with one or more -Cl groups. 101401 In certain illustrative embodiments, R' is a benzyl group substituted with one or more Br groups. [0141] In certain illustrative embodiments, R' is a benzyl group substituted with one or more -I groups. 101421 In certain illustrative embodiments, R' is a benzy group substituted with one or more OH groups. [0143] In certain illustrative embodiments, R' is a benzyl group substituted with one or more azido groups. [0144] In certain illustrative embodiments, R' is a benzyl group substituted with one or more SH groups. [0145j In certain illustrative embodiments, R' is a benzyl group substituted with one or more alkyl. 22 [0146] In certain illustrative embodiments, R' is a benzyl group substituted with one or more aryl groups. {0147] In certain illustrative embodiments, R' is a benzyl group substituted with one or more heteroalkyl groups. [01481 In certain illustrative embodiments, R' is a benzyl group substituted with one or more alkyloxyl groups. [0149J In certain illustrative embodiments, R' is a benzyl group substituted with one or more alkylthiol groups. [01501 In certain illustrative embodiments, R' is a benzyl group substituted with one or more amino groups. [0151] In certain illustrative embodiments, R' is a benzyl group substituted with one or more hydroxylamino groups. 10152] In certain illustrative embodiments, R' is a benzyl group substituted with one or more N alkylamino groups. [01531 In certain illustrative embodiments, R' is a benzyl group substituted with one or more N,N-dialkylamino groups. [0154] In certain illustrative embodiments, R' is a benzyl group substituted with one or more N,N-dimethylamino groups. [01551 In certain illustrative embodiments, R' is a benzyl group substituted with one or more acyl groups. [0156] In certain illustrative embodiments, R' is a benzyl group substituted with one orr more alkyloxycarbonyl groups. groups 101571 In certain illustrative embodiments, R' is a benzyl group substituted with one or more sulfonyl groups. [0158] In certain illustrative embodiments, R' is a benzyl group substituted with one or more urea groups. 101591 In certain illustrative embodiments, R' is a benzyl group substituted with one or more NO 2 groups. [0160] In certain illustrative embodiments, R' is a benzyl group substituted with one or more triazolyl groups. 101611 In another embodiment, R" is hydrogen. In another embodiment, R" is an alkyl group. In another embodiment, R" is an alkoxy group. In another embodiment, R" is an alkylalkoxy 23 group. In another embodiment, R" is an alkenyl group. In another embodiment, R" is alkynyl group. In another embodiment, R" is an aryl group. In another embodiment, R" is aryloxy group. In another embodiment, R" is benzyl group. In another embodiment, R" is heteroaryl group. In another embodiment, R" is heterocycloalkyl group. In another embodiment, R" is a cycloalkyl group. In another embodiment, R" is a benzyl group. [01621 In certain illustrative embodiments, R" is a benzyl group substituted with one or more -F groups. 101631 In certain illustrative embodiments, R" is a benzyl group substituted with one or more Cl groups. [0164] In certain illustrative embodiments, R" is a benzyl group substituted with one or more Br groups. 101651 In certain illustrative embodiments, R" is a benzyl group substituted with one or more -I groups. [0166] In certain illustrative embodiments, R" is a benzyl group substituted with one or more OH groups. [01671 In certain illustrative embodiments, R" is a benzyl group substituted with one or more azido groups. [0168] In certain illustrative embodiments, R" is a benzyl group substituted with one or more SH groups. [0169] In certain illustrative embodiments, R" is a benzyl group substituted with one or more alkyl. [0170] In certain illustrative embodiments, R" is a benzyl group substituted with one or more aryl groups. 101711 In certain illustrative embodiments, R" is a benzyl group substituted with one or more heteroalkyl groups. [01721 In certain illustrative embodiments, R" is a benzy group substituted with one or more alkyloxyl groups. [0173] In certain illustrative embodiments, R" is a benzyl group substituted with one or more alkylthiol groups. 101741 In certain illustrative embodiments, R" is a benzyl group substituted with one or more amino groups. 24 10175] In certain illustrative embodiments, R" is a benzyl group substituted with one or more hydroxylamino groups. [0176] In certain illustrative embodiments, R" is a benzyl group substituted with one or more N alkylamino groups. [0177] In certain illustrative embodiments, R" is a benzyl group substituted with one or more N,N-dialkylamino groups. [0178] In certain illustrative embodiments, R" is a benzyl group substituted with one or more N,N-dimethylamino groups. [01791 In certain illustrative embodiments, R" is a benzyl group substituted with one or more acyl groups. 101801 In certain illustrative embodiments, R" is a benzyl group substituted with one or more alkyloxycarbonyl groups. groups [0181]- In certain illustrative embodiments, R" is a benzyl group substituted with one or more sulfonyl groups. 101821 In certain illustrative embodiments, R" is a benzyl group substituted with one or more urea groups. [0183J In certain illustrative embodiments, I" is a benzyl group substituted with one or more NO 2 groups. [0184] In certain illustrative embodiments, R" is a benzyl group substituted with one or more triazolyl groups. [0185] In another embodiment, the invention encompasses compositions and formulations for treating or preventing diseases or disorders comprising a compound of Formula (II): -Ri R2 N N R N N N N R 5 (II) 25 or pharmaceutically acceptable salts and prodrugs thereof, wherein R, R2, R3, R4, and R' are each independently a hydrogen; hydroxyl; substituted or unsubstituted: cyclic and acyclic alkyl group, cyclic and acyclic alkenyl groupcyclic and acyclic alkynyl group, aryl group, alkylaryl group, arylalkyl group, benzyl group, cyclic and acyclic heteroalkyl group, heteroaryl group; -C(O)R 3 ; -C(S)R 3 ; -S(O)R 3 ; -S(O) 2

R

3 ;

-C(O)NR

4 R'; -C(S)NR 3

R

4 ; -C(X)YR R 6 ; -p-D-ribosyl; -a-D-ribosyl; -p-L-ribosyl; -a-L ribosyl; 2'-deoxy-p-D-ribosyl; 2'-deoxy-p-L-ribosyl; 2'-deoxy-a-D-ribosyl; 2'-deoxy-a L-ribosyl; and ribose or deoxyribose sugars substituted with one or more halogens; R' and R3 or R2 and R4 can also form a ring with one or more C, S, 0, N atoms such that R' and. R3 or R2 and R4 together include R7 R7 is a hydrogen; hydroxyl; substituted and unsubstuted: cyclic and acyclic alkyl group, group, alkenyl group, alkynyl group, aryl group, aryloxy group, alkylary group, aryalkyl group, heteroaryl group, heterocycloalkyl group; -C(O)alkyl; -C(O)alkenyl; -C(O)alkynyl; C(O)aryl; -C(O)benzyl; -C(O)NR 3

R

4 ; -C(S)alkyl; -C(S)alkenyl; -C(S)alkynyl; -C(S)aryl; -C(S)benzyl; -C(S)NR 3

R

4 ; -C(X)YR'R 2 ; wherein X is 0, N, or S; Y is 0, CH 2 , NH, or S; Z is CH, N, P, or C; -- is a single bond or double bond; wherein if -- is a double bond, R2 or R 7 is independently 0, S, or NH; and n is 1, 2, 3, or 4. [0186] In certain illustrative embodiments, Ri, R 2 , R 3 , R 4 , and R5 are each independently a substituted benzyl, alkyl, aryl, cycloalkyl, heteroaryl, or heterocycloalkyl with one ore more substituents, such as, but not limited to, -H, -F, -Cl, -Br, -I, -OH, azido, -SH, alkyl, aryl, 26 heteroalky, alkyoxyl, alkylthiol, amino, hydroxylamino, N-alkylamino, -N,N-dialkylamino, N,N-dimethylamino, acyl, alkyloxycarbonyl, sulfonyl, urea, -NO 2 , triazolyl. 101871 In one embodiment, R' is hydrogen. In another embodiment, R' is an alkyl group. In another embodiment, R' is an alkoxy group. In another embodiment, R' is an alkylalkoxy group. In another embodiment, R' is an alkenyl group. In another embodiment, R' is alkynyl group. In another embodiment, R' is an aryl group. In another embodiment, R' is aryloxy group. In another embodiment, R' is benzyl group. In another embodiment, R' is heteroaryl group. In another embodiment, R' is heterocycloalkyl group. In another embodiment, R' is a cycloalkyl group. In another embodiment, R' is a benzyl group. [0188J In certain illustrative embodiments, R' is a benzyl group substituted with one or more -F groups. [0189J In certain illustrative embodiments, R' is a benzyl group substituted with one or more -Cl groups. [0190] In certain illustrative embodiments, R is a benzyl group substituted with one or more Br groups. [0191] In certain illustrative embodiments, R' is a benzyl group substituted with one or more -J groups. [0192] In certain illustrative embodiments, R' is a benzyl group substituted with one or more OH groups. [0193J In certain illustrative embodiments, R' is a benzyl group substituted with one or more azido groups. [01941 In certain illustrative embodiments, R is a benzyl group substituted with one or more SH groups. [01951 In certain illustrative embodiments, R is a benzyl group substituted with one or more alkyl. 101961 In certain illustrative embodiments, R is a benzyl group substituted with one or more aryl groups. [0197] In certain illustrative embodiments, R' is a benzyl group substituted with one or more heteroalkyl groups. [0198] In certain illustrative embodiments, R is a benzyl group substituted with one or more alkyloxyl groups. 27 101991 In certain illustrative embodiments, R' is a benzyl group substituted with one or more alkylthiol groups. [0200] In certain illustrative embodiments, R' is a benzyl group substituted with one or more amino groups. 102011 In certain illustrative embodiments, R' is a benzyl group substituted with one or more hydroxylamino groups. [0202J In certain illustrative embodiments, R'is a benzyl group substituted with one or more N alkylamino groups. [0203J In certain illustrative embodiments, R' is a benzyl group substituted with one or more N,N-dialkylamino groups. [02041 In certain illustrative embodiments, R' is a benzyl group substituted with one or more N,N-dimethylanino groups. [02051 In certain illustrative embodiments, R' is a benzyl group substituted with one or more acyl groups. [0206J In certain illustrative embodiments, R' is a benzyl group substituted with one or more alkyloxycarbonyl groups. groups [0207] In certain illustrative embodiments, R' is a benzyl group substituted with one or more sulfonyl groups. 102081 In certain illustrative embodiments, R' is a benzyl group substituted with one or more urea groups. [02091 In certain illustrative embodiments, R' is a benzyl group substituted with one or more NO 2 groups. [0210] In certain illustrative embodiments, R' is a benzyl group substituted with one or more triazolyl groups. [02111 In one embodiment, R2 is hydrogen. In another embodiment, R2 is an alkyl group. In another embodiment, R2 is an alkoxy group. In another embodiment, R2 is an alkylalkoxy group. In another embodiment, R2 is an alkenyl group. In another embodiment, R 2 is alkynyl group. In another embodiment, R2 is an aryl group. In another embodiment, R 2 is aryloxy group. In another embodiment, R2 is benzyl group. In another embodiment, R2 is heteroaryl group. In another embodiment, R is heterocycloalkyl group. In another embodiment, R2 is a cycloalkyl group. In another embodiment, R 2 is a benzyl group. 28 [0212] In certain illustrative embodiments, R2 is a benzyl group substituted with one or more -F groups. [0213] In certain illustrative embodiments, R2 is a benzyl group substituted with one or more -Cl groups. [02141 In certain illustrative embodiments, R2 is a benzyl group substituted with one or more Br groups. [0215] In certain illustrative embodiments, R2 is a benzyl group substituted with one or more -I groups. [02161 In certain illustrative embodiments, R2 is a benzyl group substituted with one or more OH groups. [0217] In certain illustrative embodiments, R2 is a benzyl group substituted with one or more azido groups. [0218] In certain illustrative embodiments, R 2 is a benzyl group substituted with one or more SH groups. 102191 In certain illustrative embodiments, R2 is a benzyl group substituted with one or more alkyl. [0220] In certain illustrative embodiments, R2 is a benzyl group substituted with one or more aryl groups. [0221] In certain illustrative embodiments, R 2 is a benzyl group substituted with one or more heteroalkyl groups. [0222] In certain illustrative embodiments, R2 is a benzyl group substituted with one or more alkyloxyl groups. 10223] In certain illustrative embodiments, R2 is a benzyl group substituted with one or more alkylthiol groups. 102241 In certain illustrative embodiments, R2 is a benzyl group substituted with one or more amino groups. 102251 In certain illustrative embodiments, R2 is a benzyl group substituted with one or more hydroxylamino groups. [0226] In certain illustrative embodiments, R2 is a benzyl group substituted with one or more N alkylamino groups. 10227J In certain illustrative embodiments, R2 is a benzyl group substituted with one or more N,N-dialkylamino groups. 29 [0228] In certain illustrative embodiments, R2 is a benzyl group substituted with one or more N,N-dimethylamino groups. 10219] In certain illustrative embodiments, R 2 is a benzyl group substituted with one or more acyl groups. 102301 In certain illustrative embodiments, R2 is a benzyl group substituted with one or more alkyloxycarbonyl groups. groups 10231] In certain illustrative embodiments, R2 is a benzyl group substituted with one or more sulfonyl groups. [0232] In certain illustrative embodiments, R 2 is a benzyl group substituted with one or more urea groups. [02331 In certain illustrative embodiments, R2 is a benzyl group substituted with one or more NO 2 groups. [0234] In certain illustrative embodiments, R2 is a benzyl group substituted with one or more triazolyl groups. [02351 In one embodiment, R3 is hydrogen. In another embodiment, R3 is an alkyl group. In another embodiment, R3 is an alkoxy group. In another embodiment, R 3 is an alkylalkoxy group. In another embodiment, R3 is an alkenyl group. In another embodiment, R3 is alkynyl group. In another embodiment, R3 is an aryl group. In another embodiment, R3 is aryloxy group. In another embodiment, R3 is benzyl group. In another embodiment, R3 is heteroaryl group. In another embodiment, R3 is heterocycloalkyl group. In another embodiment, R3 is a cycloalkyl group. In another embodiment, R 3 is a benzyl group. [0236] In certain illustrative embodiments, R3 is a benzyl group substituted with one or more -F groups. [0237] In certain illustrative embodiments, R3 is a benzyl group substituted with one or more -CI groups. 102381 In certain illustrative embodiments, R3 is a benzyl group substituted with one or more Br groups. [02391 In certain illustrative embodiments, R3 is a benzyl group substituted with one or more -I groups. [0240J In certain illustrative embodiments, R3 is a benzyl group substituted with one or more OH groups. 30 [0241] In certain illustrative embodiments, R 3 is a benzyl group substituted with one or more azido groups. [02421 In certain illustrative embodiments, R3 is a benzyl group substituted with one or more SH groups. [0243] In certain illustrative embodiments, R3 is a benzyl group substituted with one or more alkyl. [02441 In certain illustrative embodiments, R 3 is a benzyl group substituted with one or more aryl groups. 102451 In certain illustrative embodiments, R3 is a benzyl group substituted with one or more heteroalkyl groups. 102461 In certain illustrative embodiments, R3 is a benzyl group substituted with one or more alkyloxyl groups. [0247] In certain illustrative embodiments, R 3 is a benzyl group substituted with one or more alkylthiol groups. 102481 In certain illustrative embodiments, R3 is a benzyl group substituted with one or more amino groups. [0249] In certain illustrative embodiments, R 3 is a benzyl group substituted with one or more hydroxylamino groups. [02501 In certain illustrative embodiments, R 3 is a benzy group substituted with one or more N alkylamino groups. [02511 In certain illustrative embodiments, R is a benzyl group substituted with one or more N,N-dialkylamino groups. [02521 In certain illustrative embodiments, R 3 is a benzyl group substituted with one or more N,N-dimethylamino groups. 102531 In certain illustrative embodiments, R 3 is a benzyl group substituted with one or more acyl groups. [0254) In certain illustrative embodiments, R 3 is a benzyl group substituted with one or more alkyloxycarbonyl groups. groups 10255] In certain illustrative embodiments, R 3 is a benzyl group substituted with one or more sulfonyl groups. [0256] In certain illustrative embodiments, R3 is a benzyl group substituted with one or more urea groups. 31 [0257] In certain illustrative embodiments, R3 is a benzyl group substituted with one or more NO 2 groups. 10258] In certain illustrative embodiments, R3 is a benzyl group substituted with one or more triazolyl groups. f0259J In one embodiment, R4 is hydrogen. In another embodiment, R 4 is an alkyl group. In another embodiment, R 4 is an alkoxy group. In another embodiment, R 4 is an alkylalkoxy group. In another embodiment, R 4 is an alkenyl group. In another embodiment, R 4 is alkynyl group. In another embodiment, R 4 is an aryl group. In another embodiment, R 4 is aryloxy group. In another embodiment, R4 is benzyl group. In another embodiment, R 4 is heteroaryl group. In another embodiment,~R4 is heterocycloalkyl group. In another embodiment, R 4 is a cycloalkyl group. In another embodiment, R4 is a benzyl group. [02601 In certain illustrative embodiments, R 4 is a benzyl group substituted with one or more -F groups. 10261] In certain illustrative embodiments, R4 is a benzyl group substituted with one or more -Cl groups. [0262] In certain illustrative embodiments, R 4 is a benzyl group substituted with one or more Br groups. [02631 In certain illustrative embodiments, R 4 is a benzyl group substituted with one or more -I groups. [0264] In certain illustrative embodiments, R4 is a benzyl group substituted with one or more OH groups. 10265] In certain illustrative embodiments, R4 is a benzyl group substituted with one or more azido groups. 10266] In certain illustrative embodiments, R4 is a benzyl group substituted with one or more SH groups. [02671 In certain illustrative embodiments, R is a benzyl group substituted with one or more alkyl. 10268] In certain illustrative embodiments, R4 is a benzyl group substituted with one or more aryl groups. [02691 In certain illustrative embodiments, R4 is a benzyl group substituted with one or more heteroalkyl groups. 32 [0270 In certain illustrative embodiments, R 4 is a benzyl group substituted with one or more alkyloxyl groups. 102711 In certain illustrative embodiments, R4 is a benzyl group substituted with one or more alkylthiol groups. 102721 In certain illustrative embodiments, R 4 is a benzyl group substituted with one or more amino groups. 102731 In certain illustrative embodiments, R 4 is a benzyl group substituted with one or more hydroxylamino groups. [02741 In certain illustrative embodiments, R 4 is a benzyl group substituted with one or more N alkylamino groups. 102751 In certain illustrative embodiments, R 4 is a benzyl group substituted with one or more N,N-dialkylamino groups. [02761 In certain illustrative embodiments, R4 is a benzyl group substituted with one or more N,N-dimethylamino groups. [0277] In certain illustrative embodiments, R4 is a benzyl group substituted with one or more acyl groups. [0278] In certain illustrative embodiments, R4 is a benzyl group substituted with one or more alkyloxycarbonyl groups. groups [0279] In certain illustrative embodiments, R 4 is a benzyl group substituted with one or more sulfonyl groups. [0280J In certain illustrative embodiments, R4 is a benzyl group substituted with one or more urea groups. [02811 In certain illustrative embodiments, R 4 is a benzyl group substituted with one or more NO 2 groups. [02821 In certain illustrative embodiments, R 4 is a benzyl group substituted with one or more triazolyl groups. [0283] In one embodiment, R 5 is hydrogen. In another embodiment, R 5 is an alkyl group. In another embodiment, R 5 is an alkoxy group. In another embodiment, RW is an alkylalkoxy group. In another embodiment, R 5 is an alkenyl group. In another embodiment, R 5 is alkynyl group. In another embodiment, R 5 is an aryl group. In another embodiment, R 5 is aryloxy group. In another embodiment, R 5 is benzyl group. In another embodiment, R 5 is heteroaryl group. In 33 another embodiment, R 5 is heterocycloalkyl group. In another embodiment, R 5 is a cycloalkyl group. In another embodiment, R 5 is a benzyl group. [0284J In certain illustrative embodiments, R 5 is a benzyl group substituted with one or more -F groups. [02851 In certain illustrative embodiments, R 5 is a benzyl group substituted with one or more -Cl groups. [02861 In certain illustrative embodiments, R5 is a benzyl group substituted with one or more Br groups. [02871 In certain illustrative embodiments, R 5 is a benzyl group substituted with one or more -I groups. [0288] In certain illustrative embodiments, R 5 is a benzyl group substituted with one or more OH groups. 102891 In certain illustrative embodiments, R5 is a benzyl group substituted with one or more azido groups. 102901 In certain illustrative embodiments, R 5 is a benzyl group substituted with one or more SH groups. [02911 In certain illustrative embodiments, R 5 is a benzyl group substituted with one or more alkyl. 102921 In certain illustrative embodiments, R5 is a benzyl group substituted with one or more aryl groups. [0293] In certain illustrative embodiments, R 5 is a benzyl group substituted with one or more heteroalkyl groups. [0294] In certain illustrative embodiments, R5 is a benzyl group substituted with one or more alkyloxyl groups. [02951 In certain illustrative embodiments, R 5 is a benzyl group substituted with one or more alkylthiol groups. [0296J In certain illustrative embodiments, R5 is a benzyl group substituted with one or more amino groups. 10297] In certain illustrative embodiments, R5 is a benzyl group substituted with one or more hydroxylamino groups. 102981 In certain illustrative embodiments, R 5 is a benzyl group substituted with one or more N alkylamino groups. 34 102991 In certain illustrative embodiments, R 5 is a benzyl group substituted with one or more N,N-dialkylamino groups. [03001 In certain illustrative embodiments, R5 is a benzyl group substituted with one or more N,N-dimethylamino groups. [03011 In certain illustrative embodiments, Rs is a benzyl group substituted with one or more acyl groups. 10302] In certain illustrative embodiments, R5 is a benzyl group substituted with one or more alkyloxycarbonyl groups. groups [03031 In certain illustrative embodiments, R 5 is a benzyl group substituted with one or more sulfonyl groups. [03041 In certain illustrative embodiments, R5 is a benzyl group substituted with one or more urea groups. 103051 In certain illustrative embodiments, R 5 is a benzyl group substituted with one or more NO 2 groups. 10306] In certain illustrative embodiments, R5 is a benzyl group substituted with one or more triazolyl groups. [0307] In another embodiment, the invention encompasses compositions and formulations for treating or preventing diseases or disorders comprising a compound of Formula (III): R' 0 R N / R 31-"N N R 4 N N R5 (III) or pharmaceutically acceptable salts and prodrugs thereof, wherein R', R, R4, and R' are each independently a hydrogen; hydroxyl; substituted or unsubstituted: cyclic and acyclic alkyl group, cyclic and acyclic alkenyl group, cyclic and acyclic 35 alkynyl group, aryl group, alkylaryl group, arylalkyl group, benzyl group, cyclic and acyclic heteroalkyl group, heteroaryl group; -C(O)R 3 ; -C(S)R 3 ; -S(O)R 3 ; -S(O) 2

R

3 ;

-C(O)NR

4 R; -C(S)NR 3

R

4 ; -C(X)YRR'; -p-D-ribosyl; -c-D-ribosyl; -p-L-ribosyl; -a-L ribosyl; 2'-deoxy-p-D-ribosyl; 2'-deoxy-p-L-ribosyl; 2'-deoxy-a-D-ribosyl; 2'-deoxy-a L-ribosyl; and ribose or deoxyribose sugars substituted with one or more halogens; R' and R3 can also form a ring with one or more C, S, 0, N atoms such that R' and R3 together include R7 R is a hydrogen; hydroxyl; substituted and unsubstuted: cyclic and acyclic alkyl group, group, alkenyl group, alkynyl group, aryl group, aryloxy group, alkylary group, aryalkyl group, heteroaryl group, heterocycloalkyl group; -C(Q)alkyl; -C(O)alkenyl; -C(O)alkynyl; -C(O)aryl; -C(O)benzyl; -C(O)NR 3 R4; -C(S)alkyl; -C(S)alkenyl; -C(S)alkynyl; -C(S)aryl; -C(S)benzyl; -C(S)NR 3

R

4 ; -C(X)YR'R 2 ; wherein X is 0, N, or S; Y is 0, CH 2 , NH, or S; Z is CH, N, P, or C; ------ is a single bond or double bond; wherein if ---- is a double bond, R2 or R 7 is independently 0, S, or NH; and n is 1, 2, 3, or 4. [03081 In certain illustrative embodiments, R', R3, R4, and R' are not all hydrogen. [0309] In certain illustrative embodiments, R, R3, R4, and R5 are each independently are a substituted benzyl, alkyl, aryl, cycloalkyl, heteroaryl, or heterocycloalkyl with one ore more substituents, such as, but not limited to, -H, -F, -Cl, -Br, -I, -OH, azido, -SH, alkyl, aryl, heteroalky, alkyoxyl, alkylthiol, amino, hydroxylamino, N-alkylamino, -N,N-dialkylamino, N,N-dimethylamino, acyl, alkyloxycarbonyl, sulfonyl, urea, -NO 2 , triazolyl. 36 [0310J In one embodiment, R' is hydrogen. In another embodiment, R' is an alkyl group. In another embodiment, R' is an alkoxy group. In another embodiment, R' is an alkylalkoxy group. In another embodiment, R' is an alkenyl group. In another embodiment, R' is alkynyl group. In another embodiment, R' is an aryl group. In another embodiment, R' is aryloxy group. In another embodiment, R' is benzyl group. In another embodiment, R' is heteroaryl group. In another embodiment, R' is heterocycloalkyl group. In another embodiment, R' is a cycloalkyl group. In another embodiment, R' is a benzyl group. [0311] In certain illustrative embodiments, R' is a benzyl group substituted with one or more -F groups. [03121 In certain illustrative embodiments, R' is a benzyl group substituted with one or more -Cl groups. {0313] In certain illustrative embodiments, R' is a benzyl group substituted with one or more Br groups. [0314] In certain illustrative embodiments, R' is a benzyl group substituted with one or more -I groups. [0315] In certain illustrative embodiments, R' is a benzyl group substituted with one or more OH groups. [0316J In certain illustrative embodiments, R' is a benzyl group substituted with one or more azido groups. 10317] In certain illustrative embodiments, R' is a benzyl group substituted with one or more SH groups, 103181 In certain illustrative embodiments, R' is a benzyl group substituted with one or more alkyl. [0319] In certain illustrative embodiments, R' is a benzyl group substituted with one or more aryl groups. [0320] In certain illustrative embodiments, R' is a benzyl group substituted with one or more heteroalkyl groups. [0321] In certain illustrative embodiments, R' is a benzyl group substituted with one or more alkyloxyl groups. [0322] In certain illustrative embodiments, R' is a benzyl group substituted with one or more alkylthiol groups. 37 [0323] In certain illustrative embodiments, R is a benzyl group substituted with one or more amino groups. [0324J In certain illustrative embodiments, R is a benzyl group substituted with one or more hydroxylamino groups. [0325] In certain illustrative embodiments, R' is a benzyl group substituted with one or more N alkylamino groups. 10326] In certain illustrative embodiments, R1 is a benzyl group substituted with one or more N,N-dialkylamino groups. 10327J In certain illustrative embodiments, R is a benzyl group substituted with one or more N,N-dimethylamino groups. [0328] In certain illustrative embodiments, R' is a benzyl group substituted with one or more acyl groups. [03291 In certain illustrative embodiments, R1 is a benzyl group substituted with one or more alkyloxycarbonyl groups. groups [03301 In certain illustrative embodiments, R is a benzyl group substituted with one or more sulfonyl groups. [0331] In certain illustrative embodiments, R is a benzyl group substituted with one or more urea groups. [03321 In certain illustrative embodiments, R' is a benzyl group substituted with one or more NO 2 groups. [0333J In certain illustrative embodiments, R' is a benzyl group substituted with one or more triazolyl groups. [0334] In one embodiment, R3 is hydrogen. In another embodiment, R3 is an alkyl group. In another embodiment, R3 is an alkoxy group. In another embodiment, R7 is an alkylalkoxy group. In another embodiment, R3 is an alkenyl group. In another embodiment, R3 is alkynyl group. In another embodiment, R 3 is an aryl group. In another embodiment, R3 is aryloxy group. In another embodiment, R3 is benzyl group. In another embodiment, R3 is heteroaryl group. In another embodiment, R 3 is heterocycloalkyl group. In another embodiment, R3 is a cycloalkyl group. In another embodiment, R 3 is a benzyl group. 10335] In certain illustrative embodiments, R3 is a benzyl group substituted with one or more -F groups. 38 [0336J In certain illustrative embodiments, R 3 is a benzyl group substituted with one or more -Cl groups. [0337] In certain illustrative embodiments, R 3 is a benzyl group substituted with one or more Br groups. (03381 In certain illustrative embodiments, R 3 is a benzyl group substituted with one or more -I groups. [0339] In certain illustrative embodiments, R 3 is a benzyl group substituted with one or more OH groups. [0340] In certain illustrative embodiments, R3 is a benzyl group substituted with one or more azido groups. [0341] In certain illustrative embodiments, R3 is a benzyl group substituted with one or more SH groups. [03421 In certain illustrative embodiments, R 3 is a benzyl group substituted with one or more alkyl. [03431 In certain illustrative embodiments, R3 is a benzyl group substituted with one or more aryl groups. [03441 In certain illustrative embodiments, R3 is a benzyl group substituted with one or more heteroalkyl groups. [0345] In certain illustrative embodiments, R3 is a benzyl group substituted with one or more alkyloxyl groups. 103461 In certain illustrative embodiments, R3 is a benzyl group substituted with one or more alkylthiol groups. 103471 In certain illustrative embodiments, R3 is a benzyl group substituted with one or more amino groups. 10348] In certain illustrative embodiments, R3 is a benzyl group substituted with one or more hydroxylamino groups. [03491 In certain illustrative embodiments, R3 is a benzyl group substituted with one or more N alkylamino groups. [03501 In certain illustrative embodiments, R3 is a benzyl group substituted with one or more N,N-dialkylanino groups. [0351J In certain illustrative embodiments, R 3 is a benzyl group substituted with one or more N,N-dimethylamino groups. 39 [0352] In certain illustrative embodiments, R 3 is a benzyl group substituted with one or more acyl groups. [03531 In certain illustrative embodiments, R3 is a benzyl group substituted with one or more alkyloxycarbonyl groups. groups 103541 In certain illustrative embodiments, R3 is a benzyl group substituted with one or more sulfonyl groups. [0355 In certain illustrative embodiments, R3 is a benzyl group substituted with one or more urea groups. 103561 In certain illustrative embodiments, R3 is a benzyl group substituted with one or more NO 2 groups. [03571 In certain illustrative embodiments, R3 is a benzyl group substituted with one or more triazolyl groups. 10358] In one embodiment, R 4 is hydrogen. In another embodiment, RW is an alkyl group. In another embodiment, R is an alkoxy group In another embodiment, R4 is an alkylakoxy group. In another embodiment, R4 is an alkenyl group. In another embodiment, R 4 is alkynyl group. In another embodiment, R 4 is an aryl group. In another embodiment, R4 is aryloxy group. In another embodiment, R4 is benzyl group. In another embodiment, R4 is heteroaryl group. In another embodiment, R 4 is heterocycloalkyl group. In another embodiment, R 4 is a cycloalkyl group. In another embodiment, R4 is a benzyl group. [03591 In certain illustrative embodiments, 4 is a benzyl group substituted with one or more -F groups. [03601 In certain illustrative embodiments, R4 is a benzyl group substituted with one or more -Cl groups. [0361] In certain ilhistrative embodiments, R4 is a benzyl group substituted with one or more Br groups. [0362] In certain illustrative embodiments, R4 is a benzyl group substituted with one or more -1 groups. [0363] In certain illustrative embodiments, R4 is a benzyl group substituted with one or more OH groups. [03641 In certain illustrative embodiments, R4 is a benzyl group substituted with one or more azido groups. 40 10365] In certain illustrative embodiments, R 4 is a benzyl group substituted with one or more SH groups. [03661 In certain illustrative embodiments, R4 is a benzyl group substituted with one or more alkyl. 103671 In certain illustrative embodiments, R4 is a benzyl group substituted with one or more aryl groups. 103681 In certain illustrative embodiments, R4 is a benzyl group substituted with one or more heteroalkyl groups. [03691 In certain illustrative embodiments, R4 is a benzyl group substituted with one or more alkyloxyl groups. [0370] In certain illustrative embodiments, Rt is a benzyl group substituted with one or more alkylthiol groups. [03711 In certain illustrative embodiments, R4 is a benzyl group substituted with one or more amino groups. [03721 In certain illustrative embodiments, R4 is a benzyl group substituted with one or more hydroxylamino groups. 10373] In certain illustrative embodiments, R 4 is a benzyl group substituted with one or more N alkylamino groups. [03741 In certain illustrative embodiments, R4 is a benzyl group substituted with one or more N,N-dialkylamino groups. [03751 In certain illustrative embodiments, R4 is a benzyl group substituted with one or more N,N-dimethylamino groups. [03761 In certain illustrative embodiments, R4 is a benzyl group substituted with one or more acyl groups. [0377] In certain illustrative embodiments, R4 is a benzyl group substituted with one or more alkyloxycarbonyl groups. groups [0378] In certain illustrative embodiments, R4 is a benzyl group substituted with one or more sulfonyl groups. [0379] In certain illustrative embodiments, Rt is a benzyl group substituted with one or more urea groups. [0380] In certain illustrative embodiments, R 4 is a benzyl group substituted with one or more NO 2 groups. 41 [0381] In certain illustrative embodiments, R 4 is a benzyl group substituted with one or more triazolyl groups. 10382) In one embodiment, R 5 is hydrogen. In another embodiment, R 5 is an alkyl group. In another embodiment, R 5 is an alkoxy group. In another embodiment, R 5 is an alkylalkoxy group. In another embodiment, R 5 is an alkenyl group. In another embodiment, R 5 is alkynyl group. In another embodiment, R5 is an aryl group. In another embodiment, RS is aryloxy group. In another embodiment, R 5 is benzyl group. In another embodiment, R 5 is heteroaryl group. In another embodiment, R 5 is heterocycloalkyl group. In another embodiment, R 5 is a cycloalkyl group. In another embodiment, R 5 is a benzyl group. [03831 In certain illustrative embodiments, R 5 is a benzyl group substituted with one or more -F groups. 103841 In certain illustrative embodiments, Rs is a benzyl group substituted with one or more -Cl groups. [0385] In certain illustrative embodiments, R5 is a benzyl group substituted with one or more Br groups. 103861 In certain illustrative embodiments, R 5 is a benzyl group substituted with one or more -I groups. [03871 In certain illustrative embodiments, R 5 is a benzyl group substituted with one or more OH groups. [03881 In certain illustrative embodiments, R5 is a benzyl group substituted with one or more azido groups. 103891 In certain illustrative embodiments, Rs is a benzyl group substituted with one or more SH groups. 103901 In certain illustrative embodiments, R 5 is a benzyl group substituted with one or more alkyl. 103911 In certain illustrative embodiments, R 5 is a benzyl group substituted with one or more aryl groups. [03921 In certain illustrative embodiments, R 5 is a benzyl group substituted with one or more heteroalkyl groups. [0393] In certain illustrative embodiments, R 5 is a benzyl group substituted with one or more alkyloxyl groups. 42 10394] In certain illustrative embodiments, R 5 is a benzyl group substituted with one or more alkylthiol groups. [0395] In certain illustrative embodiments, R 5 is a benzyl group substituted with one or more amino groups. 103961 In certain illustrative embodiments, R 5 is a benzyl group substituted with one or more hydroxylamino groups. 103971 In certain illustrative embodiments, R is a benzyl group substituted with one or more N alkylamino groups. f0398] In certain illustrative embodiments, R5 is a benzyl group substituted with one or more N,N-dialkylamino groups. [03991 In certain illustrative embodiments, R5 is a benzyl group substituted with one or more N,N-dimethylamino groups. 104001 In certain illustrative embodiments, R' is a benzyl group substituted with one or more acyl groups. 104011 In certain illustrative embodiments, R 5 is a benzyl group substituted with one or more alkyloxycarbonyl groups. groups [0402] In certain illustrative embodiments, R 5 is a benzyl group substituted with one or more sulfonyl groups. [0403] In certain illustrative embodiments, R- is a benzyl group substituted with one or more urea groups. [0404] In certain illustrative embodiments, R5 is a benzyl group substituted with one or more NO 2 groups. [0405] In certain illustrative embodiments, R 5 is a benzyl group substituted with one or more triazolyl groups. [0406] In another embodiment, the invention encompasses compositions and formulations for treating or preventing diseases or disorders comprising a compound of Formula (IV): 43 /0 NN N N R 3R 4 N N (IV) or pharmaceutically acceptable salts and prodrugs thereof, wherein R3 and R4 are each independently a hydrogen; hydroxyl; substituted or unsubstituted: cyclic and acyclic alkyl group, cyclic and acyclic alkenyl group, cyclic and acyclic alkynyl group, aryl group, alkylaryl group, arylalkyl group, benzyl group, cyclic and acyclic heteroalkyl group, heteroaryl group; -C(O)R 3 ; -C(S)R 3 ; -S(O)R 3 ; -S(O) 2

R

3 ; -C(O)NR 4 R;

-C(S)NR

3

R

4 ; -C(X)YRR; -p-D-ribosyl; -c-D-ribosyl; -p-L-ribosyl; -a-L-ribosyl; 2' deoxy-p-D-ribosyl; 2'-deoxy-p-L-ribosyl; 2'-deoxy-a-D-ribosyl; 2'-deoxy-a-L-ribosyl; and ribose or deoxyribose sugars substituted with one or more halogens. 104071 In certain illustrative embodiments, R3 and R 4 are both not hydrogen. [0408] In certain illustrative embodiments, R 3 and R 4 are each independently are a substituted benzyl, alkyl, aryl, cycloalkyl, heteroaryl, or heterocycloalkyl with one ore more substituents, such as, but not limited to, -H, -F, -Cl, -Br, -I, -OH, azido, -SH, alkyl, aryl, heteroalky, alkyoxyl, alkylthiol, amino, hydroxylamino, N-alkylamino, -N,N-dialkylamino, -N,N-dimethylamino, acyl, alkyloxycarbonyl, sulfonyl, urea, -NO 2 , triazolyl. 10409] In one embodiment, R3 is hydrogen. In another embodiment, R3 is an alkyl group. In another embodiment, R3 is an alkoxy group. In another embodiment, R3 is an alkylalkoxy group. In another embodiment, R3 is an alkenyl group. In another embodiment, R3 is alkynyl group. In another embodiment, R3 is an aryl group. In another embodiment, R 3 is aryloxy group. In another embodiment, R3 is benzyl group. In another embodiment, R3 is heteroaryl group. In another embodiment, R3 is heterocycloalkyl group. In another embodiment, R3 is a cycloalkyl group. In another embodiment, R3 is a benzyl group. 104101 In certain illustrative embodiments, R3 is a benzyl group substituted with one or more -F groups. 44 104111 In certain illustrative embodiments, R 3 is a benzyl group substituted with one or more -Cl groups. [0412] In certain illustrative embodiments, R 3 is a benzyl group substituted with one or more Br groups. 104131 In certain illustrative embodiments, R 3 is a benzyl group substituted with one or more -I groups. [04141 In certain illustrative embodiments, R 3 is a benzyl group substituted with one or more OH groups. [0415] In certain illustrative embodiments, R3 is a benzyl group substituted with one or more azido groups. [0416] In certain illustrative embodiments, R3 is a benzyl group substituted with one or more SH groups. [0417] In certain illustrative embodiments, R3 is a benzyl group substituted with one or more alkyl. 10418] In certain illustrative embodiments, R3 is a benzyl group substituted with one or more aryl groups. [04191 In certain illustrative embodiments, R3 is a benzyl group substituted with one or more heteroalkyl groups. [0420] In certain illustrative embodiments, R? is a benzyl group substituted with one or more alkyloxyl groups. [04211 In certain illustrative embodiments, R3 is a benzyl group substituted with one or more alkylthiol groups. 104221 In certain illustrative embodiments, R3 is a benzyl group substituted with one or more amino groups. [04231 In certain illustrative embodiments, R3 is a benzyl group substituted with one or more hydroxylamino groups. [0424] In certain illustrative embodiments, R 3 is a benzyl group substituted with one or more N alkylamino groups. [0425] In certain illustrative embodiments, R 3 is a benzyl group substituted with one or more N,N-dialkylamino groups. [0426] In certain illustrative embodiments, R3 is a benzyl group substituted with one or more N,N-dimethylamino groups. 45 [0427J in certain illustrative embodiments, R 3 is a benzyl group substituted with one or more acyl groups. [0428] In certain illustrative embodiments, R 3 is a benzyl group substituted with one or more alkyloxycarbonyl groups. groups 10429] In certain illustrative embodiments, R3 is a benzyl group substituted with one or more sulfonyl groups. [04301 In certain illustrative embodiments, R 3 is a benzyl group substituted with one or more urea groups. 104311 In certain illustrative embodiments, R 3 is a benzyl group substituted with one or more NO 2 groups. [0432] In certain illustrative embodiments, R3 is a benzyl group substituted with one or more triazolyl groups. [0433] In one embodiment, R 4 is hydrogen. In another embodiment, R 4 is an alkyl group. In another embodiment, R4 is an alkoxy group. In another embodiment, R 4 is an alkylalkoxy group. In another embodiment, R 4 is an alkenyl group. In another embodiment, R4 is alkynyl group. In another embodiment, R4 is an aryl group. In another embodiment, R4 is aryloxy group. In another embodiment, R4 is benzyl group. In another embodiment, R4 is heteroaryl group. In another embodiment, R4 is heterocycloalkyl group. In another embodiment, R 4 is a cycloalkyl group. In another embodiment, R 4 is a benzyl group. [04341 In certain illustrative embodiments, RW is a benzyl group substituted with one or more -F groups. [0435] In certain illustrative embodiments, R 4 is a benzyl group substituted with one or more -Cl groups. [0436] In certain illustrative embodiments, R 4 .is a benzyl group substituted with one or more Br groups. [0437] In certain illustrative embodiments, R 4 is a benzyl group substituted with one or more -I groups. [0438] In certain illustrative embodiments, R4 is a benzyl group substituted with one or more OH groups. [0439] In certain illustrative embodiments, R4 is a benzyl group substituted with one or more azido groups. 46 [0440] In certain illustrative embodiments, R 4 is a benzyl group substituted with one or more SH groups. [04411 In certain illustrative embodiments, R4 is a benzyl group substituted with one or more alkyl. 104421 In certain illustrative embodiments, R is a benzyl group substituted with one or more aryl groups. [04431 In certain illustrative embodiments, R 4 is a benzyl group substituted with one or more heteroalkyl groups. [0444] In certain illustrative embodiments, R 4 is a benzyl group substituted with one or more alkyloxyl groups. [0445] In certain illustrative embodiments, R 4 is a benzyl group substituted with one or more alkylthiol groups. 10446] In certain illustrative embodiments, R 4 is a benzyl group substituted with one or more amino groups. [0447] In certain illustrative embodiments, R4 is a benzyl group substituted with one or more hydroxylamino groups. [0448] In certain illustrative embodiments, R 4 is a benzyl group substituted with one or more N alkylamino groups. [0449] In certain illustrative embodiments, R 4 is a benzyl group substituted with one or more N,N-dialkylamino groups. [0450] In certain illustrative embodiments, R 4 is a benzyl group substituted with one or more N,N-dimethylamino groups. 10451] In certain illustrative embodiments, R 4 is a benzyl group substituted with one or more acyl groups. [0452] In certain illustrative embodiments, R4 is a benzyl group substituted with one or more alkyloxycarbonyl groups. groups [0453] In certain illustrative embodiments, R 4 is a benzyl group substituted with one or more sulfonyl groups. (04541 In certain illustrative embodiments, R4 is a benzyl group substituted with one or more urea groups. [04551 In certain illustrative embodiments, R4 is a benzyl group substituted with one or more NO 2 groups. 47 104561 In certain illustrative embodiments, R 4 is a benzyl group substituted with one or more triazolyl groups. 104571 In another embodiment, the invention encompasses compositions and formulations for treating or preventing diseases or disorders comprising a compound of Formula (V): N 0 N R5 N NC N N N (V) or pharmaceutically acceptable salts and prodrugs thereof, wherein R3, R4, and R5 are each independently a hydrogen; hydroxyl; substituted or unsubstituted: cyclic and acyclic alkyl group, cyclic and acyclic alkenyl group, cyclic and acyclic alkynyl group, aryl group, alkylaryl group, -arylalkyl group, benzyl group, cyclic and acyclic heteroalkyl group, heteroaryl group; -C(O)R 3 ; -C(S)R 3 ; -S(O)R 3 ; -S(O) 2

R

3 ; -C(O)NR 4

R

5 ;

-C(S)NR

3

R

4 ; -C(X)YRR 6 ; -p-D-ribosyl; -ct-D-ribosyl; -p-L-ribosyl; -a-L-ribosyl; 2' deoxy-p-D-ribosyl; 2'-deoxy-p-L-ribosyl; 2'-deoxy-c-D-ribosyl; 2'-deoxy-a-L-ribosyl; and ribose or deoxyribose sugars substituted with one or more halogens. 10458] In certain illustrative embodiments, R3, R4, and R 5 are not each hydrogen. 10459] In certain illustrative embodiments, R 3 , R4, and R 5 are each independently are a substituted benzyl, alkyl, aryl, cycloalkyl, heteroaryl, or heterocycloalkyl with one ore more substituents, such as, but not limited to, -H, -F, -Cl, -Br, -I, -OH, azido, -SH, alkyl, aryl, heteroalky, alkyoxyl, alkylthiol, amino, hydroxylamino, N-alkylamino, -N,N-dialkylamino, -N,N-dimethylamino, acyl, alkyloxycarbonyl, sulfonyl, urea,

-NO

2 , triazolyl. -[04601 In one embodiment, R3 is hydrogen. In another embodiment, R 3 is an alkyl group. In another embodiment, R 3 is an alkoxy group. In another embodiment, RW is an alkylalkoxy group. In another embodiment, R3 is an alkenyl group. In another embodiment, R3 is alkynyl group, In another.embodiment, R3 is an aryl group. In another embodiment, R3 is aryloxy group. In 48 another embodiment, R 3 is benzyl group. In another embodiment, R 3 is heteroaryl group. In another embodiment, R 3 is heterocycloalkyl group. In another embodiment, RW is a cycloalkyl group. In another embodiment, R3 is a benzyl group. [0461] In certain-illustrative embodiments, RW is a benzyl group substituted with one or more -F groups. [0462] In certain illustrative embodiments, R3 is a benzyl group substituted with one or more -CI groups. [04631 In certain illustrative embodiments, R is a benzyl group substituted with one or more Br groups. 104641 In certain illustrative embodiments, R3 is a benzyl group substituted with one or more -1 groups. [0465] In certain illustrative embodiments, R3 is a benzyl group substituted with one or more OH groups. [04661 In certain illustrative embodiments, R 3 is a benzyl group substituted with one or more azido groups. [0467] In certain illustrative embodiments, R3 is a benzyl group substituted with one or more SH groups. [0468] In certain illustrative embodiments, R3 is a benzyl group substituted with one or more alkyl. (0469] In certain illustrative embodiments, R3 is a benzyl group substituted with one or more aryl groups. [0470] In certain illustrative embodiments, R 3 is a benzyl group substituted with one or more heteroalkyl groups. [0471] In certain illustrative embodiments, R3 is a benzyl group substituted with one or more alkyloxyl groups. [0472] In certain illustrative embodiments, R3 is a benzyl group substituted with one or more alkylthiol groups. [0473] In certain illustrative embodiments, R3 is a benzyl group substituted with one or more amino groups. [0474] In certain illustrative embodiments, R3 is a benzyl group substituted with one or more hydroxylamino groups. 49 104751 In certain illustrative embodiments, R 3 is a benzyl group substituted with one or more N alkylamino groups. [04761 In certain illustrative embodiments, R 3 is a benzyl group substituted with one or more N,N-dialkylamino groups. [0477) In certain illustrative embodiments, R3 is a benzyl group substituted with one or more N,N-dimethylanino groups. 104781 In certain illustrative embodiments, R3 is a benzyl group substituted with one or more acyl groups. 10479) In certain illustrative embodiments, R3 is a benzyl group substituted with one or more alkyloxycarbonyl groups. groups [0480] In certain illustrative embodiments, R 3 is a benzyl group substituted with one or more sulfonyl groups. 104811 In certain illustrative embodiments, R3 is a benzyl group substituted with one or more urea groups. [0482J In certain illustrative embodiments, R3 is a benzyl group substituted with one or more NO 2 groups. [0483] In certain illustrative embodiments, R 3 is a benzyl group substituted with one or more triazolyl groups. [04841 In one embodiment, R4 is hydrogen. In another embodiment, R is an alkyl group. In another embodiment, R4 is an alkoxy group. In another embodiment, R 4 is an alkylalkoxy group. In another embodiment, R4 is an alkenyl group. In another embodiment, R4 is alkynyl group. In another embodiment, R4 is an aryl group. In another embodiment, R 4 is aryloxy group. In another embodiment, R4 is benzyl group. In another embodiment, R 4 is heteroaryl group. In another embodiment, R4 is heterocycloalkyl group. In another embodiment, R 4 is a cycloalkyl group. In another embodiment, R4 is a benzyl group. [0485] In certain illustrative embodiments, R4 is a benzyl group substituted with one or more -F groups. 104861 In certain illustrative embodiments, R4 is a benzyl group substituted with one or more -CI groups. [0487 In certain illustrative embodiments, R4 is a benzyl group substituted with one or more Br groups. 50 10488] In certain illustrative embodiments, R 4 is a benzyl group substituted with one or more -I groups. [04891 In certain illustrative embodiments, R 4 is a benzyl group substituted with one or more OH groups. [04901 In certain illustrative embodiments, R 4 is a benzyl group substituted with one or more azido groups. [0491] In certain illustrative embodiments, R 4 is a benzyl group substituted with one or more SH groups. [0492] In certain-illustrative embodiments, R4 is a benzyl group substituted with one or more alkyl. 104931 In certain illustrative embodiments, R 4 is a benzyl group substituted with one or more aryl groups. (0494] In certain illustrative embodiments, R 4 is a benzyl group substituted with one or more heteroalkyl groups. [0495J In certairi illustrative embodiments, R 4 is a benzyl group substituted with one or more alkyloxyl groups. [0496] In certain illustrative embodiments, R4 is a benzyl group substituted with one or more alkylthiol groups. [04971 In certain illustrative embodiments, R4 is a benzyl group substituted with one or more amino groups. [0498] In certain illustrative embodiments, R 4 is a benzyl group substituted with one or more hydroxylamino groups. [04991 In certain illustrative embodiments, R 4 is a benzyl group substituted with one or more N alkylamino groups. 105001 In certain illustrative embodiments, RW is a benzyl group substituted with one or more N,N-dialkylamino groups. [0501] In certain illustrative embodiments, R4 is a benzyl group substituted with one or more N,N-dimethylamino groups. [0502] In certain illustrative embodiments, R4 is a benzyl group substituted with one or more acyl groups. 10503] In certain illustrative embodiments, R4 is a benzyl group substituted with one or more alkyloxycarbonyl groups. groups 51 105041 In certain illustrative embodiments, R 4 is a benzyl group substituted with one or more sulfonyl groups. 10505] In certain illustrative embodiments, R 4 is a benzyl group substituted with one or more urea groups. [05061 In certain illustrative embodiments, R 4 is a benzyl group substituted with one or more NO 2 groups. [0507] In certain illustrative embodiments, R 4 is a benzyl group substituted with one or more triazolyl groups. [05081 In one embodiment, R5 is hydrogen. In another embodiment, R5 is an alkyl group. In another embodiment, R' is an alkoxy group. In another embodiment, R 5 is an alkylalkoxy group. In another embodiment, R5 is an alkenyl group. In another embodiment, R5 is alkynyl group. In another embodiment;R 5 is an aryl group. In another embodiment, R5 is aryloxy group. In another embodiment, R5 is benzyl group. In another embodiment, R is heteroaryl group. In another embodiment, R is heterocycloalkyl group. In another embodiment, R5 is a cycloalkyl group. In another embodiment, R 5 is a benzyl group. [0509] In certain illustrative embodiments, R5 is a phenyl or a benzyl group substituted with one or more -F groups. [05101 In certain illustrative embodiments, R is a phenyl or a benzyl group substituted with one or more -Cl groups. .10511] In certain illustrative embodiments, R' is a phenyl or a benzyl group substituted with one or more -Br groups. 105121 In certain illustrative embodiments, R 5 is a phenyl or a benzyl group substituted with one or more -I groups. 105131 In certain illustrative embodiments, R is a phenyl or a benzyl group substituted with one or more OH groups. 105141 In certain illustrative embodiments, R is a phenyl or a benzyl group substituted with one or more azido groups. [05151 In certain illustrative embodiments, R is a phenyl or a benzyl group substituted with one or more -SH groups. 105161 In certain illustrative embodiments, R5 is a phenyl or a benzyl group substituted with one or more alkyl. 52 [0517] In certain illustrative embodiments, R 5 is a phenyl or a benzyl group substituted with one or more aryl groups. [05181 In certain illustrative embodiments, R 5 is a phenyl or a benzyl group substituted with one or more heteroalkyl groups. [05191 In certain illustrative embodiments, R 5 is a phenyl or a benzyl group substituted with one or more alkyloxyl groups. (05201 In certain illustrative embodiments,"R 5 is a phenyl or a benzyl group substituted with one or more alkylthiol groups.

[0521] In certain illustrative embodiments, R 5 is a phenyl or a benzyl group substituted with one or more amino groups. 10522] In certain illustrative embodiments, R 5 is a phenyl or a benzyl group substituted with one or more hydroxylamino groups. [05231 In certain illustrative embodiments, R 5 is a phenyl or a benzyl group substituted with one or more N-alkylanino groups. [05241 In certain illu'stratiVe embodiments, R 5 is a phenyl or a benzyl group substituted with one or more -N,N-dialkylamino groups. [05251 In certain illustrative embodiments, R 5 is a phenyl or a benzyl group substituted with one or more -N,N-dimethylamino groups. [0526] In certain illustrative embodiments, R 5 is a phenyl or a benzyl group substituted with one or more acyl groups. [0527] In certain illustrative embodiments, R 5 is a phenyl or a benzyl group substituted with one or more alkyloxycarbonyl groups. groups [0528] In certain illustrative embodiments, R 5 is a phenyl or a benzyl group substituted with one or more sulfonyl groups. 105291 In certain illustrative embodiments, R 5 is a phenyl or a benzyl group substituted with one or more urea groups. 10530] In certain illustrative embodiments, R is a phenyl or a benzyl group substituted with one or more -NO 2 groups. 105311 In certain illustrative embodiments, R 5 is a phenyl or a benzyl group substituted with one or more triazolyl groups. [05321 Illustrative examples of compounds that are encompassed by Formulas I-V and that arc useful in the methods of the invention include, but are not limited to: 53 MeO N 0 OMe N N WzZ N 3;

H

3 CO N

OCH

3 N N 11;

H

3 CO

H

3 CO H 0 CH 3 N N >1 NY N N- N 12; 54

(H

3

C)

2 N HN

OCH

3 N N HN N N N 13; -Hago C, N OCH 3 r N NOCH N N N 14; Cl N 0

OCH

3 N N 21; 55 - HI 3 CO H~H3 NH

OCH

3 NY NN--1 N N HO HO0 23;

H

3 CO 0 OCHa N N

NO

2 25; 56 N NN 27; c2 i'N N N C2 0 -C02H 101; 57 0 2 N N 0 NO 2 NN N N 102; N~ N F N N 103; CI N CI N N 104; Br Br N N 105; 58 NN N N-Z N 106; H2N N NH 2 N N N N 107;

(HC)

2 N N N N(CH 3 )2 N N N N 108;

H

3 CHN N / 0 NHCHa N N 109; 59 HO N 0 OH N N 110; HS N SH N N 111;

N

3 N N 3 N N 112; H3C 0

CH

3 N N NN 113; 60 Ph 0Ph N N 114;

H

3 CS N /N SCH 3 Ph N N N N 115; OHN N0NH6H Nj N N 116; Ph NP/ N 117; 61 N N N It3CX( 2 C) N /NA (CH2)XCHS N j N x= I1- 17 119; 0 HsCY(8 2 C)Q~ (CHi 2

)XCH

3 Nj. N N x= 1- 17 y=1I -17 120;

H

3 Cy(H 2 C)O , FN -o 0(GH2XCH3 >1 N> N > N N y= I - 10 121; 62 N02 /0 N

NO

2 N, N 122;

CH

3 N N

OCH

3 N N 123; 0 rA N N- NN OH N N 124; 0 SHN N N N SH- Nzs. . N 125; 63 NN N N F N N 126; N N >N N .01 N N 127; r N Br N N 128; ~N ,N N1 N N, N 129; 64

NH

2 0 N(C 3) N N 131 NN

NH

2 N N 130;

N(CH

3

)

2 0 NtN j N - -, N N(CH3) 2 131;

N

3 0 Nt N N 3 N, N 132;,

H

3 0 N N

OH

3 N 133; 65 Ph 0 Nx N NN Ph N 134; CH3 NN >1 Nj N SCH3 135; N HO H 0 NJ Nj N N NHOH W, - 136;

NHCH

3 N /N I N

NHCH

3 N 137; 66 0

CH

3 0 N O N N

H

3 C 0 138; 0 CH3 ,y 0 N N N; N

H

3 C 0 139; 67 N NN 1400 NN NNN 141; HaCO N N H 0 N N N N NN N 142N 141; 68 3

C

H

3 CO O2N H 0 NO2 N N 143; - H 3 CO

H

2 N N IN 2 N N *N~ N 144; 69

H

3 CO H3C N 0 CH3 N N N N NZ N 145;

H

3 CO HO N OH N N 0 146; 70

H

3 CO HS 0 N SH N

N

147;

H

3 CO

H

3 C N0 CH3 SN Nt N>~N 148; 71

H

3 CO N N NN N N 149;

H

3 CO Ph I N Ph N N 72 N 72

H

3 CO H3CS / 0

SCH

3 'N N 151;

H

3 CO HtCHN N N0NHCH 3 N N 152;

H

3 CO

(H

3

C)

2 N N N0N(CH 3

)

2 N N -- _ NN 153; 73

H

3 CO HsC NCHa N N 154;

H

3 CO Ph N Ph N N N 155; 73C

(CNN(CH

2 ) CH N N 156; 74 0 N- N

H

3 C (CH N (CH2)2 CH 3 N N 157; 0 N N

H

3 C NN (CH2)3 CH3 N N 158; SN N

H

3 C (CH N N

(CH

2

)

3 CH3 N N 159; 0 N N H C ( C N N (C H 2

)

8

H

3 CH/ N N 160; 75 NH3C (CH.NA (CH 2)1 CH 0 N N H C161; 00 oN N 162; 0 HC N N (CH 2

)

1 6 o N 0 163; 0 A Nf ~4 CI! 3

)

12 <N//Ny (CH 2 )je

H

3 C CH3 N N s 164; 76 0 NJ N ,! N 165; NJ N N 166; H 0C N N 167; 77 H3CO HN NO2 N N 168; H3CO HNN H N NH2 N N 169; 78

H

3 CO N NOH HN N 170;

H

3 CO HN / SH N N 171;

H

3 CO H

SH

H N /NSH N N 172; 79

H

3 C HN/ N N 173; F N 0 OCH 3 HN/ N N N 174;

(H

3

C)

2 N O N OCH3 N N 175; 80

(H

3 C)2N

N(CH

3

)

2 HC~ HN N N N 176;

(H

3

C)

2 N

N(CH

3

)

2

N(CH

3

)

2 HNH 0OCH3 HN/ N N>~N 177;

(H

3

C)

2 N

N(CH

3

)

2

N(CH

3

)

2 HN NH2 rKN N N N 178; 81

(H

3

C)

2 N N(CH3)2 HN NH 2 N N 179;

(H

3

C)

2 N N NH2 HN N 180;

(H

3

C)

2 N I H0 OH HN / N N N 181; 82

(H

3

C)

2 N HN N N N 182;

H

3 CHN 0 SH N HN N N N 183;

(H

3

C)

2 N N 0 CH3 HN/ N N N 184; 83

(H

3

C)

2 N H Ph H N N HN / 185;

(H

3

C)

2 N 0

SCH

3 NN N N. 186;

(H

3

C)

2 N H N

NHCH

3 N N 187; 84 0 N/ 2'-deoxy-P-D-ribosyl /)2-ex-PDroy 188; 0 <N / N N 1-D-ribosyl P--ioy 189;

H

3 CO .N N N N / ~ N 2 'deoxy-P-D-ribosyI NN 190; 0 .xN N NN 2'-deoxy-aL-L-ribosyl /2'-deoxy-a.LD-ibosy N N 191; 85

H

3 CO N OCHa N N NJN OH 192; and

H

3 CO N N

OCH

3 >N N N N S02CH 3 193. 86 10533J It will be understood that above compounds are illustrative only and not intended to limit the scope of the claims to only those compounds. 105341 The compounds of the invention can be synthesized by organic chemistry techniques known to those of ordinary skill in the art, for example, generally as described in the synthesis in Scheme I below. Scheme 1 OMe- R Me o R2 R 2 N

H

2 N NH 2 IN R 3 N N IN R I P \$,

H

2 N NH 2 N~... TFA, 60 OC, 3-6 h HN N 4 6 steps N 78-81% 11; R 1 =OMe; R 2 = R 3 = H OMe 13; R, N(Me) 2 ; R 2 = R 3 = H 3 14; R 1

R

2 = R 3 = OMe [0535] An examination of the literature revealed that the target 5:7:5 heterocyclic ring system is yet unknown. Scheme 2 illustrates the first entry into such a ring system employing an illustrative representative example 3, containing a removable p-methoxybenzyl (PMB) group attached to each of the two imidazole rings. 87 Scheme 2 EtOs 9 H MeO NCXNHZ (OEt3CH NC N PMBNH 2 N 1,4-doxane, PhNH 2 -HCI (cat), HN NC NH 2 reflux, 65% NC NH 2 EtOH, rt, 3 h, 65% W H 4 5 NC 11N NC NH2 6 DBU (cat.), EtOH, rt O 2 h, 67% N HN H OMe N CN CN N NH 2 PMBNCO / \ N NH 2 8 MeCN, 0 *C-rt, M 6h OMe

H

2 N NCH2Ph-OMe(p) MeCN DBU (cat.), rt, 1 h, N N 0 75% MeOH 10 N Me 00 N N NH (OEt) 3 CH (,N N N NH 2 MeCN,

H

2 S0 4 (cat.), OMe reflux, 1.5 h. 76% N OMe OMe 9 3 [0536] Generally, an illustrative compound of the invention can be synthesized by heating diaminomaleonitrile 4 with triethyl orthoformate in dioxane yielded formimidate 5. (See, e.g., Sun, Z.; Hosmane, R. S. Synth Commun. 2001, 31, 549). The reaction of 5 with p methoxybenzylamine catalyzed by aniline hydrochloride formed formimidine 6 (See, e.g., 88 Yahya-Zadeh, A.; Booth, B. L. Synth. Commun. 2001, 31, 3225), which underwent intramolecular cyclization in the presence of DBU to form imidazole derivative 7. (See, e.g., Yahyazadeh, A.; Sharifi, Z. Phosphorus, Sulfur, Silicon, Relat. Elem. 2006, 181, 1339). The treatment of latter with p-methoxybenzyl isocyanate resulted into a mixture of urea 8 and 9. (See, e.g., Dias, A. M.; Cabral, L; Proenca, M. F.; Booth, B. L. J Org.Chem. 2002, 67, 5546). The complete coversion of 8 into 9 was achieved by treating the mixture with DBU in acetonitrile. (Id.). The reaction of isolated 9 with triethyl orthoformate yielded the target heterocycle 3. In certain embodiments, the reported rearrangement of a compound such as 8 into an oxopurine such as 10 was not observed. In an illustrative embodiment, a rearrangement has been limited to the use of N-tosylisocyanate, but not others. (Id.). This was further corroborated by the facile ring-closure of 9 to form 3. All intermediates and final product were fully characterized by spectroscopic and analytical data. (See Example Section). [0537] The core tricyclic structure of 3 containing 14 n electrons is aromatic by the Hfckel rule. Nevertheless, with six nitrogen atoms and a conjugated carbonyl group present in the heterocyclic ring system, compound 3 is considerably electrophilic. In order to explore this aspect a little further, compound 3 was reacted with a few carbon and nitrogen nucleophiles. Illustrative examples of the carbon nucleophiles attempted include anisole, N,N-dimethylaniline, and 1,2,3-trimethoxybenzene, all of which contain electron-donating substituent(s) on their aromatic rings. Thus, the reaction of a mixture of 3 (1 mmol), anisole (5 mL), and TFA (10 mL) at 60 *C for 3 h (Scheme 3) formed a novel product 11 which was isolated, purified (81%) and characterised. 89 Scheme 3 Me MeO Me o 0 NA M1 N N N N N N. TFA,60 0 C,3h,81% HN N 11 OMe 3 105381 In order to illucidate the pathway of formation of 11 from 3, the latter (1 mmol) was treated with a mixture of TFA (10 mL) and anisole (5 mL)16 at rt for 12 h (Scheme 4), which yielded a mixture of 11 (10%) and 12 (60%) which was found to be an adduct of anisole by spectroscopic and analytical data. Suprisingly, 12 was converted into 11 when heated with TFA at 60 *C for 1 h. This suggests that the reaction proceeds by first addition of anisole, followed by selective cleavage of the N-3 PMB group. As TFA is often used to remove the PMB group from heterocyclic rings, the observed deprotection of one of the imidazole rings under these conditions is not totally surprising. (See, e.g., Miki, Y.; Hachiken, H.; Kashima, Y.; Sugimura, W.; Yanase, N. Heterocycles 1998, 48, 1). Scheme 4 Me Me MeO OMe MeO ~H ! 111HN4

N

3 - N b N TFA, rt, N TFA. 60 C, N 12 h, 60% h/ \h,80% N N N_/ HN N / \ 12 11 OMe 10539] The generality of the above reaction was studied using two other electron-rich carbon nucleophiles, including N,N-dimethylaniline and 1,2,3-trimethoxybenzene. Thus, when 3 (1 90 mmol) was heated separately (Scheme 5) at 60 *C for 6 h with N,N-dimethylaniline (5 mL) or 1,2,3-trimethoxy benzene (5 mL) in TFA (10 mL), compound 13 (78%) or 14 (80%), was formed, respectively. Scheme 5 Me Me e M MeO Me Me M & N M e 1 I e O Me ,!:r Me0e /\ N 3- N N TFA. 60 *C, TFA. 60 "C, . N6 h, 78% 3 h, 80%/N N h8 3.O <,,N I N HN Ng' HN N 13 14 [05401 In certain illustrative embodiments, the structures of 3 and 11-14 were determined by ID and 2D NMR experiments (some important peaks and correlations are presented in Figure 2 with an example of 12; and Tables 1-3), including HMQC, HMBC and DEPT experiments. In the HMBC spectra, H-5 showed the correlations with C-6a and C-11; H-i' showed correlation with C-8, C-3' and C-7'; C-8 showed correlations with H-I'. The addition of anisole/1,2,3 trimethoxybenzene /N,N-dimethylaniline at position 9a was determined by the correlation of H 2"(or/and) and H-6" with C-9a; two-bond coupling enhancement between C-9a and H-9 (N) and H-9 (N) and C-8. 5.3. Therapeutic Uses of the Compounds of the Invention 10541] In accordance with the invention, a composition or formulation comprising a compound of the invention and optionally a pharmaceutically acceptable vehicle, is administered to a mammal, preferably a human, experiencing one or more of the following disorders: conditions caused by uncontrolled cell growth, hyperproliferation of cells, tumor growth, and cancers. 105421 The invention also encompasses methods for treating or preventing lung cancer, pancreatic cancer, leukemia, breast cancer, liver cancer, kidney cancer, ovarian cancer, human glioblastoma and prostate cancer, which comprises administering to a mammal in need of such treatment or prevention a therapeutically or prophylactically effective amount of a composition comprising a compound of Formula I-V, or a pharmaceutically acceptable salt or prodrug thereof, and a pharmaceutically acceptable vehicle. [05431 In certain embodiments, a composition or formulation comprising a compound of Formula I-V is useful in treating or preventing conditions caused by uncontrolled cell growth. 91 [0544] In certain embodiments, a composition or formulation comprising a compound of Formula I-V is useful in killing abnormal or cancerous cells while simultaneously not affecting healthy or normal cells. [0545] In certain embodiments, a composition or formulation comprising a compound of Formula I-V acts as a cytotoxic agent. [0546] In certain embodiments, a composition or formulation comprising a compound of Formula I-V acts as apoptotic agent. [05471 In one embodiment, "treatment" or "treating" refers to an amelioration of a disease or disorder, or at least one discernible symptom thereof. In another embodiment, "treatment" or "treating" refers to an amelioration of at least one measurable physical parameter, not necessarily discernible by the patient. In yet another embodiment, "treatment" or "treating" refers to inhibiting the progression of a disease or disorder, either physically, e.g., stabilization of a discernible symptom, physiologically, e.g., stabilization of a physical parameter, or both. In yet another embodiment, "treatment" or "treating" refers to delaying the onset of a disease or disorder. [0548] In certain embodiments, the compositions of the invention are administered to a patient, preferably a human, as a preventative measure against such diseases. As used herein, "prevention" or "preventing" refers to a reduction of the risk of acquiring a given disease or disorder. In a preferred mode, the compositions of the present invention are administered as a preventative measure to a patient. 5.4. Therapeutic/Prophylactic Administration and Compositions and Formulations of the Invention [0549] Due to the activity of the compounds of the invention, the compounds are advantageously useful in veterinary and human medicine, As described in Section 5.3 above, the compounds of the invention are useful for the treatment or prevention of conditions conditions caused by uncontrolled cell growth, hyperproliferation of cells, tumor growth, and cancers, for example, lung cancer, pancreatic cancer, leukemia, breast cancer, liver cancer, kidney cancer, human glioblastoma and prostate cancer. [05501 The invention provides methods of treatment and prophylaxis by administration to a patient of a therapeutically effective amount of a composition comprising a compound of the 92 invention. The patient is a mammal, including, but not limited, to an animal such a cow, horse, sheep, pig, chicken, cat, dog, mouse, rat, rabbit, guinea pig, and is more preferably a human. [0551) The present compositions, which comprise one or more compounds of the invention, are preferably administered intravenously or orally. [0552] However, suitable dosage ranges of the compounds of the invention are generally about 0.0001 milligram to 2000 milligrams of a compound of the invention per kilogram body weight. In specific preferred embodiments of the invention, the oral dose is about 0.001 milligram to about 1500 milligrams per kilogram body weight, more preferably about 0.01 milligram to about 1000 milligrams per kilogram body weight, more preferably about 0.1 milligram to about 500 milligrams per kilogram body weight, and yet more preferably about 1 milligram to about 100 milligrams per kilogram body weight. 10553] The compounds of the invention may also be administered by any other convenient route, for example, by infusion or bolus injection, by absorption through epithelial or mucocutaneous linings (e.g., oral mucosa, rectal and intestinal mucosa, etc.) and may be administered together with another biologically active agent. Administration can be systemic or local. Various delivery systems are known, e.g., encapsulation in liposomes, microparticles, microcapsules, capsules, etc., and can be used to administer a compound of the invention. In certain embodiments, more than one compound of the invention is administered to a patient. Methods of administration include but are not limited to intradermal, intramuscular, intraperitoneal, intravenous, subcutaneous, intranasal, epidural, oral, sublingual, intranasal, intracerebral, intravaginal, transdermal, rectally, by inhalation, or topically, particularly to the ears, nose, eyes, or'skin. The preferred mode of administration is left to the discretion of the practitioner, and will depend in-part upon the site of the medical condition. In most instances, administration will result in the release of the compounds of the invention into the bloodstream. 10554] In specific embodiments, it may be desirable to administer one or more compounds of the invention locally to the area in need of treatment. This may be achieved, for example, and not by way of limitation, by local infusion during surgery, topical application, e.g., in conjunction with a wound dressing after surgery, by injection, by means of a catheter, by means of a suppository, or by means of an implant, said implant being of a porous, non-porous, or gelatinous material, including membranes, such as sialastic membranes, or fibers. In one embodiment, administration can be by direct injection at the site (or former site) of an atherosclerotic plaque tissue. 93 [0555J Pulmonary administration can also be employed, e.g., by use of an inhaler or nebulizer, and formulation with an aerosolizing agent, or via perfusion in a fluorocarbon or synthetic pulmonary surfactant. In certain embodiments, the compounds of the invention can be formulated as a suppository, with traditional binders and vehicles such as triglycerides. 105561 In another embodiment, the compounds of the invention can be delivered in a vesicle, in particular a liposome (see Langer, 1990, Science 249:1527-1533; Treat et al., in Liposomes in the Therapy of Infectious Disease and Cancer, Lopez-Berestein and Fidler (eds.), Liss, New York, pp. 353-365 (1989); Lopez-Berestein, ibid., pp. 317-327; see generally ibid.). [0557] In yet another embodiment, the compounds of the invention can be delivered in a controlled release system. In one embodiment, a pump may be used (see Langer, supra; Sefton, 1987, CRC Crit. Ref Biomed Eng. 14:20 1; Buchwald et al., 1980, Surgery 88:507 Saudek et al., 1989, N. Engl. J Med. 321:574). In another embodiment, polymeric materials can be used (see Medical Applications of Controlled Release, Langer and Wise (eds.), CRC Pres., Boca Raton, Fla. (1974); Controlled Drug Bioavailability, Drug Product Design and Performance, Smolen and Ball (eds.), Wiley, New York (1984); Ranger and Peppas, 1983, J Macromol Sci. Rev. Macromol. Chem. 23:61; see also Levy et al., 1985, Science 228:190; During et al., 1989, Ann NeuroL 25:351; Howard et al., 1989, J Neurosurg. 71:105). In yet another embodiment, a controlled-release system can be placed in proximity of the target of the compounds of the invention, e.g., the liver, thus requiring only a fraction of the systemic dose (see, e.g., Goodson, in Medical Applications of Controlled Release, supra, vol. 2, pp. 115-138 (1984)). Other controlled-release systems discussed in the review by Langer, 1990, Science 249:1527-1533) may be used. 10558J The present compositions will contain a therapeutically effective amount of a compound of the invention, optionally more than one compound of the invention, preferably in purified form, together with a suitable amount of a pharmaceutically acceptable vehicle so as to provide the form for proper administration to the patient. [0559) In a specific embodiment, the term "pharmaceutically acceptable" means approved by a regulatory agency of the Federal or a state government or listed in the U.S. Pharmacopeia or other generally recognized pharmacopeia for use in animals, and more particularly in humans. The term "vehicle" refers to a diluent, adjuvant, excipient, or carrier with which a compound of the invention is administered. Such pharmaceutical vehicles can be liquids, such as water and oils, including those of petroleum, animal, vegetable or synthetic origin, such as peanut oil, 94 soybean oil, mineral oil, sesame oil and the like. The pharmaceutical vehicles can be saline, gum acacia, gelatin, starch paste, talc, keratin, colloidal silica, urea, and the like. In addition, auxiliary, stabilizing, thickening, lubricating and coloring agents may be used. When administered to-a patient, the compounds of the invention and pharmaceutically acceptable vehicles are preferably sterile. Water is a preferred vehicle when the compound of the invention is administered intravenously. Saline solutions and aqueous dextrose and glycerol solutions can also be employed as liquid vehicles, particularly for injectable solutions. Suitable pharmaceutical vehicles also include excipients such as starch, glucose, lactose, sucrose, gelatin, malt, rice, flour, chalk, silica gel, sodium stearate, glycerol monostearate, talc, sodium chloride, dried skim milk, glycerol, propylene, glycol, water, ethanol and the like. The present compositions, if desired, can also contain minor amounts of wetting or emulsifying agents, or pH buffering agents. [05601 The present compositions can take the form of solutions, suspensions, emulsion, tablets, pills, pellets, capsules, capsules containing liquids, powders, sustained-release formulations, suppositories, emulsions, aerosols, sprays, suspensions, or any other form suitable for use. In one embodiment, the pharmaceutically acceptable vehicle is a capsule (see e.g., U.S. Pat. No. 5,698,155). Other examples of suitable pharmaceutical vehicles are described in "Remington's Pharmaceutical Sciences" by A. R. Gennaro. [0561] In another embodiment, the compounds of the invention are formulated in accordance with routine procedures as a pharmaceutical composition adapted for intravenous administration .to human beings. Typically, compounds of the invention for intravenous administration are solutions in sterile isotonic aqueous buffer. Where necessary, the compositions may also include a solubilizing agent. Compositions for intravenous administration may optionally include a local anesthetic such as lignocaine to ease pain at the site of the injection. Generally, the ingredients are supplied either separately or mixed together in unit dosage form, for example, as a dry lyophilized powder or water free concentrate in a hermetically sealed container such as an ampoule or sachette indicating the quantity of active agent. Where the compound of the invention is to be administered by infusion, it can be dispensed, for example, with an infusion bottle containing sterile pharmaceutical grade water or saline. Where the compound of the invention is administered by injection, an ampoule of sterile water for injection or saline can be provided so that the ingredients may be mixed prior to administration. 10562] It is preferred that the compositions of the invention be administered orally. Formulations for oral delivery may be in the form of tablets, lozenges, aqueous or oily 95 suspensions, granules, powders, emulsions, capsules, syrups, or elixirs, for example. Orally administered compositions may contain one or more optionally agents, for example, sweetening agents such as fructose, aspartame or saccharin; flavoring agents such as peppermint, oil of wintergreen, or cherry; coloring agents; and preserving agents, to provide a pharmaceutically palatable preparation. Moreover, where in tablet or pill form, the compositions may be coated to delay disintegration and absorption in the gastrointestinal tract thereby providing a sustained action over an extended period of time. Selectively permeable membranes surrounding an osmotically active driving compound are also suitable for orally administered compounds of the invention. In these later platforms, fluid from the environment surrounding the capsule is imbibed by the driving compound, which swells to displace the agent or agent composition through an aperture. These delivery platforms can provide an essentially zero order delivery profile as opposed to the spiked profiles of immediate release formulations. A time delay material such as glycerol monostearate or glycerol stearate may also be used. Oral compositions can include standard vehicles such as mannitol, lactose, starch, magnesium stearate, sodium saccharine, cellulose, magnesium carbonate, etc. Such vehicles are preferably of pharmaceutical grade. 105631 The amount of a compound of the invention that will be effective in the treatment of a particular disorder or condition disclosed herein will depend on the nature of the disorder or condition, and can be determined by standard clinical techniques. In addition, in vitro or in vivo assays may optionally be employed to help identify optimal dosage ranges. The precise dose to be employed in the compositions will also depend on the route of administration, and the seriousness of the disease or disorder, and should be decided according to the judgment of the practitioner and each patient's circumstances. However, suitable dosage ranges for oral administration are generally about about 0.001 milligram to about 200 milligrams of a compound of the invention per kilogram body weight. In specific preferred embodiments of the invention, the oral dose is about 0.01 milligram to about 100 milligrams per kilogram body weight, more preferably about 0.1 milligram to about 50 milligrams per kilogram body weight, more preferably about 0.5 milligram to about 20 milligrams per kilogram body weight, and yet more preferably about 1 milligram to about 10 milligrams per kilogram body weight. In a most preferred embodiment, the oral dose is about 5 milligrams of a compound of the invention per kilogram body weight. The dosage amounts described herein refer to total amounts administered; that is, if more than one compound of the invention is administered, the preferred dosages 96 correspond to the total amount of the compounds of the invention administered. Oral compositions preferably contain 10% to 95% active ingredient by weight. [05641 In other embodiments, a composition of the invention for oral administration includes about 0.001 milligram to about 2000 milligrams of a compound of the invention, more preferably about 0.01 milligram to about 1000 milligrams of a compound of the invention, more preferably about 0.1 milligram to about 500 milligrams of a compound of the invention, and yet more preferably about 1 milligram to about 200 milligrams of a compound of the invention. 105651 Suitable dosage ranges for parenteral, for example, intravenous (i.v.) administration are 0.01 milligram to 100 milligrams per kilogram body weight, 0.1 milligram to 35 milligrams per kilogram body weight, and 1 milligram to 10 milligrams per kilogram body weight. Suitable dosage ranges for intranasal administration are generally about 0.01 pg/kg body weight to I mg/kg body weight. Suppositories generally contain 0.01 milligram to 50 milligrams of a compound of the invention per kilogram body weight and comprise active ingredient in the range of 0.5% to 10% by weight. Recommended dosages for intradermal, intramuscular, intraperitoneal; subcutaneous, epidural, sublingual, intracerebral, intravaginal, transdermal administration or administration by inhalation are in the range of 0.001 milligram to 200 milligrams per kilogram of body weight. Suitable doses of the compounds of the invention for topical administration are in the range of 0.001 milligram to 1 milligram, depending on the area to which the compound is administered. Effective doses may be extrapolated from dose-response curves derived from in vitro or animal model test systems. Such animal models and systems are well known in the art. [05661 In other embodiments, a composition of the invention for parenteral, for example, intravenous administration includes about 0.001 milligram to about 2000 milligrams of a compound of the invention, more preferably about 0.0 1 milligram to about 1000 milligrams of a compound of the invention, more preferably about 0.1 milligram to about 500 milligrams of a compound of the invention, and yet more preferably about 1 milligram to about 200 milligrams of a compound of the invention. 10567] The invention also provides pharmaceutical packs or kits comprising one or more containers filled with one or more compounds of the invention. Optionally associated with such container(s) can be a notice in the form prescribed by a governmental agency regulating the manufacture, use or sale of pharmaceuticals or biological products, which notice reflects 97 approval by the agency of manufacture, use or sale for human administration. In a certain embodiment, the kit contains more than one compound of the invention. [0568J The compounds of the invention are preferably assayed in vitro and in vivo, for the desired therapeutic or prophylactic activity, prior to use in humans. For example, in vitro assays can be used to determine whether administration of a specific compound of the invention or a combination of compounds of the invention is preferred for treating depression, MS, incontinence, or IBS. The compounds of the invention may also be demonstrated to be effective and safe using animal model systems. 105691 Other methods will be known to the skilled artisan and are within the scope of the invention. 6. EXAMPLES [0570] The compounds of the invention showed pharmacological efficacy in treating or preventing various disorders. [0571] General. The 'H and ' 3 C NMR spectra were recorded on a JEOL-400 NMR spectrometer, operating at 400 MHZ for 'H, and 100 MHz for "C NMR. Thin layer chromatography was performed on Merck Kieselgel 60 F 2 54 (0.2 mm thickness). Flash column chromatography was performed using 32-63 mesh silica gel. Melting points were determined on a Thomas Hoover capillary melting point apparatus and are uncorrected. The high resolution mass spectra were recorded either at the Mass Spectral Analysis Service, Department of Chemistry, The Johns Hopkins University, Baltimore, MD. Anhydrous solvents were purchased and used without further drying and alcohols were dried over sodium metal, distilled, and stored over molecular sieves. EXAMPLE 1 [0572] Synthesis of ethyl (Z)-N-(2-amino-1,2-dicyanovinyl)formimidate' (5): EtOCH NCIN NC

NH

2 98 105731 A mixture of diaminomaleonitrile (4, 6.0 g, 55.5 mmol, 1 equiv) and triethyl orthoformate (9.2 mL, 55.5 mmol, 1 equiv) in dioxane (80 mL) was heated at reflux in a flask fitted with a short Vigreux column, a distillation head, a condenser, and a receiver. Ethanol mixed with 1,4-dioxane was collected continuously until the temperature in the distillation head reached 99-100 *C (approximately 20 min). The clear brown liquid in the distillation pot was allowed to cool overnight. The reaction mixture was diluted with hot diethyl ether, filtered to remove the dark brown solid impurity, and left to cool overnight to give 5 as colorless needles (6 g, 65%). IR (KBr): 3309 (N-H str.), 2247 (CN str.), 2207 (CN str.), 1636 (C=N str.), 1608, 1256 (C-O str.), 810 cm-'. 'H NMR (400 MHz, CDCl 3 ): 8 = 1.35 (t, J= 7.3 Hz, 3 H, CH 3 ), 4.25 (q, J= 7.3 Hz, 2 H, CH 2 ), 4.66 (brs, 2 H, D20-exchangable NH 2 ), 7.97 (s, 1 H, CH). 10574] Synthesis of ( 4 -methoxybenzyl)-(Z)-N-(2-amino-1,2-dicyanovinyl)formimidine (6): MeO -1 NN HN'CH N I NC N NC

NH

2 [05751 4-methoxybenzyl amine (0.92 mL, 6.70 mmol, 1.1 equiv) was added to a suspension of 5 (1 g, 6.09 mmol, I equiv) in dry EtOH which contained aniline hydrochloride (0.02 g). The mixture was stirred at room temperature until TLC showed that all the formimidate had disappeared (-3 h) and the pale yellow solid was obtained by filtration, washed with diethyl ether and dried to give 6 (1.2 g, 65%). mp: 96-98 *C, IR (KBr): 3309 (N-H str.), 2225 (CN str.), 2206 (CN str.), 1632 (C=N str.), 1591, 1511, 1247 (C-0 str.) cm". 'H NMR (400 MHz, d 6 DMSO): 8 = 3.72 (s, 3 H, OCH 3 ), 4.44 (d, J= 4.5 Hz, 2 H, CH 2 ), 6,11 (s, 2 H, D 2 0-exchangable

NH

2 ), 6.89 (d, J= 8.2 Hz, 2 H, Ar-H), 7.26 (d, J= 8.2 Hz, 2 H, Ar-H), 7.70 (d, J= 2.3 Hz, I H, CH), 8.10 (brs, 1 H, D 2 0-exchangable NH). "C NMR (100 MHz, d 6 -DMSO): S = 43.4, 55.6, 106.8, 114.2, 115.7, 116.8, 117.6, 129.7, 131.1, 150.8, 158.9. HRMS (FAB) Calcd for C 14 H1 4

N

4 0, 254.1168 (M); observed m/z 255.1115 (M+H)*. 99 [0576] Synthesis of 5-amino-l-(4-methoxybenzyl)-4-cyanoformimidoylimidazole (7): HN N CN MeO / N

NH

2 [0577] To a suspension of 6 (2.0 g) in dry EtOH (10 mL), DBU was added (1 drop). The reaction mixture was stirred 2 h at room temperature under nitrogen atmosphere until starting material was disappeared (TLC). The precipitated product was filtered, washed with diethyl ether and dried under vacuum to afford 7 as off-white solid (1.35 g, 67%). mp: 92-94 "C, IR (KBr): 3290 (N-H str.), 3122 (N-H str.), 2218 (CN str.), 1629 (C=N str.), 1549, 1515 (C-0 str.), 1254, 810 cm-. 'H NMR (400 MHz, d 6 -DMSO): 8= 3.72 (s, 3 H, OCH 3 ), 5.03 (s, 2 H, CH 2 ), 6.76 (brs, 2 H, D20-exchangable NH 2 ), 6.91 (d, J= 8.2 Hz, 2 H, Ar-H), 7.22 (d, J= 8.2 Hz, 2 H, Ar H), 7.30 (s, 1 H, Imid-H), 10.87 (s, 1 H, D20-exchangable NH). "C NMR (100 MHz, d, DMSO): 6 = 45.7, 55.7, 114.1, 114.6, 116.7, 128.8, 129.5, 132.8, 143.5, 144.7, 159.4. HRMS (FAB) Calcd for C 13

HUN

5 0, 255.1120 (M*); observed m/z 256.1113 (M+H)*. [0578] Synthesis of 4 -(1-( 4 -nethoxybenzyl)-5-amino-1H-imidazol-4-y)-1-(4-ethoxybenzyl) 5-imino-IH-imidazol-2(SH)-one (9): 0 N N N NHN OMe OMe 10579J To a suspension of 7 (1.35 g, 5.29 mmol, 1 equiv) in dry MeCN (10 mL), 4 methoxybenzyl isocyanate was added (2.16 mL, 15.87 mmol, 3 equiv) under nitrogen atmosphere at 0 *C. The reaction mixture was stirred at rt for 6 h until starting material was disappeared (TLC). The yellow precipitate was filtered, washed with diethyl ether and dried under vacuum to afford the mixture of (Z)-1-(4-methoxybenzyl)-3-((1-(4-methoxybenzyl)-5 amino-1H-imidazol-4-yl)(cyano)methylene) urea (8) and 9 as yellow solid. Further, 2-5 drops of DBU were added to a suspension of 8 and 9 and the reaction mixture was stirred for I h. The 100 deep yellow precipitate was filtered, washed with diethyl ether and dried under vacuum to afford 9 as yellow solid (1.6 g, 75%). mp: decomposed > 215-217 *C, IR: 3195 (N-H str.), 3131 (N-H str.), 1702 (C=O), 1643, 1513, 1249, 773 cm. 'H NMR (400 MHz, d-DMSO): 8 = 3.70 (s, 3 H, OCH 3 ), 3.72 (s, 3 H, OCH 3 ), 4.62 (s, 2 H, CH 2 ), 5.11 (s, 2 H, CH 2 ), 6.85 (d, J= 8.2 Hz, 2 H, Ar-H), 6.93 (d, J= 8.2 Hz, 2 H, Ar-H), 7.21 (d, J= 8.2 Hz, 2 H, Ar-H), 7.25 (d, J= 8.2 Hz, 2 H, Ar-H), 7.73 (s, I H, Imid-H), 7.90 (brs, 2 H, D20-exchangable NH 2 ), 9.77 (s, 1 H, D 2 0 exchangable NH). "C NMR (00 MHz, dr-DMSO): 8 = 41.7, 45.9, 55.6, 55.7, 114.3, 114.7, 128.2, 129.4, 129.5, 130.2, 139.5, 152.2, 157.6, 158.9, 159.5, 160.1, 167.3. HRMS (FAB) Calcd for C 2 2 H22N 6 0 3 , 418.1753 (M'); observed m/z 419.1824 (M+H)*. 105801 Synthesis of 3,7-Dihydro-3,7-bis[(4-methoxyphenyl)methyl]-2H-diimidazoj4,5 d:4',5'-f][1,3jdiazepin-2-one (3): OMe N IN NN OMe [0581] To a suspension of 9 (1.0 g, 2.39 mmol, I equiv) in MeCN (10 mL), triethyl orthoformate (2.8 g, 19.13 mmol, 8 equiv) was added followed by 2 drops of sulfuric acid. The reaction mixture was heated at reflux for 1.5 h until starting material was disappeared (TLC). The precipitated product was filtered, washed with diethyl ether and dried under vacuum to afford 3 as pale yellow solid (0.77 g, 76%). mp: 175-177 *C, IR : 1737 (C=O), 1610, 1589, 1251, 1176 cm-. 1H.NMR (400 MHz, d 6 -DMSO): S = 3.69 (s, 3 H, OCH 3 ), 3.70 (s, 3 H, OCH 3 ), 5.08 (s, 2 H, CH 2 ), 5.51 (s, 2 H, CH 2 ), 6.85 (d, J= 8.2 Hz, 2 H, Ar-H), 6.89 (d, J= 8.2 Hz, 2 H, Ar-H), 7.29 (d, J= 8.2 Hz, 2 H, Ar-H), 7.33 (d, J= 8.2 Hz, 2 H, Ar-H), 8.75 (s, I H, Ar-C=N-H), 8.92 (s, I H, Imid-H). ' 3 C NMR (100 MHz, d 6 -DMSO): S = 43.4, 47.0, 55.6, 55.7, 114.4, 114.6, 128.5, 128.8, 129.2, 129.7, 129.8, 148.9,150.3, 156.3, 159.2, 159.5, 160.2, 166.3. HRMS (FAB) Calcd for C 23

H

2 0

N

6 0 3 , 428.1597 (M*); observed m/z 429.1667 (M+H). 101 [0582) Synthesis of 1,3,7,9b-Tetrahydro-9b-(4-methoxyphenyl)-3-[(4 methoxyphenyl)methyl]-2H-diimidazo[4,5-d:4',5'-][1,3]diazepin-2-one (11): MeO OMe 0 NA N N HN H N N [05831 To a stirred suspension of 3 (0.43 g, 1 mmol) in anisole (5 mL), TFA (10 mL, dropwsie) was added. The reaction mixture'was heated at 60 *C for 3 h. TFA was evaporated on rotary evaporator after the disappearance of starting material (TLC) and excess of sodium bicarbonate was added. The reaction mixture was extracted with EtOAc (30 x 3 mL), washed with brine, dried (anhyd. Na 2

SO

4 ) and adsorbed over silica and purified through column chromatography to afford 11 as yellowish white solid (0.34 g, 81%). mp: 223-225 *C, IR: 1743 (C=O str.), 1619, 1513, 1249 (C-0 str.) emt. 'H NMR (400 MHz, d 6 -DMSO): S= 3.67 (s, 3 H, OCH 3 ), 3.71 (s, 3 H, OCH 3 ), 4.63 (dd, J= 15.1, 18.3 Hz , 2 H, CH 2 ), 6.68 (d, J= 8.6 Hz, 2 H, Ar-H), 6.80 (d, J= 9.16 Hz, 2 H, Ar-H), 6.86 (d, J= 8.7 Hz, 2 H, Ar-H), 7.19 (d, J= 8.6 Hz, 2 H, Ar-H), 7.53 (s, I H, Ar-CH=N-), 7.87 (s, f H, Imid-H), 9.82 (brs, 1 H, D20-exchangable NH), 13 C NMR (100 MHz, d 6 -DMSO): 8= 42.9, 55.6, 55.7, 64.6, 114.4, 114.5, 121.1, 127.7, 129.0, 129.4, 134.8, 137.5, 145.9, 154.3, 155.8, 159.1, 159.7. HRMS (FAB) Calcd for C22H 20

N

5 0 3 , 416.1597 (M); observed m/z 417.1669 (M+H)*. 105841 Synthesis of 1,3,7,9b-Tetrahydro-9b-(4-methoxyphenyl)-3,7-bis[(4 methoxyphenyl)methyl]-2H-diimidazo[4,5-d:4',5'-][1,3Jdiazepin-2-one (12): MeO Me HN N N NN N OMe 102 105851 To a stirred suspension of 3 (0.43 g, I mmol) in anisole (5 mL), TFA (10 mL, dropwsie) was added and the reaction mixture was stirred at rt for 12 h. TFA was evaporated on rotary evaporator after the disappearance of starting material (TLC) and excess of sodium bicarbonate was added. The reaction mixture was extracted with EtOAc (30 x 3 mL), washed with brine, dried (anhyd. Na2SO 4 ) and adsorbed over silica and purified through column chromatography to afford 12 (0.32 g, 60%, yellowish solid) and 11 (0.042 g, 10%). mp: 95-97 "C, IR: 1754 (C=O str.), 1612, 1512, 1250 (C-0 str.) cm 1 . 'H NMR (400 MHz, CDC 3 ): 8 = 3.68 (s, 3 H, OCH 3 ), 3.77 (s, 3 H, OCR 3 ), 3.77 (s, 3 H, OCH 3 ), 4.72 (s, 2 H, CH 2 ), 5.13 (q, J= 14.2 Hz, 2 H, CH 2 ), 6.61 (d, J= 8.6 Hz, 2 H, Ar-H), 6.72 (d, J= 8.6 Hz, 2 H, Ar-H), 6.79-6.83 (m, 4H, Ar-H), 7.08 (d, J= 8.6 Hz, 2 H, Ar-H), 7.33 (d, J= 8.6 Hz, 2 H, Ar-H), 7.65 (s, I H, Ar-CH=N-), 7.69 (s, 1 H, Imid-H), 9.47 (brs, I H, D20-exchangable NH), 1 3 C NMR (100 MHz, CDC 3 ): 6= 43.4,46.9, 55.3, 55.4, 64.2, 114.0, 114.1, 114.3, 121.0, 127.4, 128.4, 129.0, 129.9, 134.4,-138.3, 146.6, 154.6, 156.2, 159.2, 159.4, 159.6. HRMS (FAB) Caled for C 30

H

2 8

N

6 0 4 , 536.2172 (M); observed m/z 537.2235 (M+H)*. [0586] Synthesis of 1,3,7,9b-Tetrahydro-9b-(4-NN-dimethylaminophenyl)-3-[(4 methoxyphenyl)methylj-2H-diimidazo[4,5-d:4',5'-fJ [1,3]diazepin-2-one (13): Me .e' OMe 0 N N HNN [0587] To a stirred suspension of 3 (0.43 g, 1 mmol) in N,N-dimethylaniline (5 mL), TFA (10 mL, dropwsie) was added. The reaction mixture was heated at 60 "C for 6 h. TFA was evaporated on rotary evaporator after the disappearance of starting material (TLC) and excess of sodium bicarbonate was added. The reaction mixture was extracted with EtOAc (30 x 3 mL), washed with brine, dried (anhyd. Na2SO 4 ) and adsorbed over silica and purified through column chromatography to afford 13 as yellowish white solid (0.33 g, 78%); mp: decomposed > 225 *C, IR : 1730 (C=0 str.), 1610, 1525, 1248 (C-O str.) cm'. 'H NMR (400 MHz, d6-DMSO): 8= 2.81 (s, 6 H, N(CH 3

)

2 ), 3.71 (s, 3 H, OCH 3 ), 4.62 (dd, J= 15.1, 18.3 Hz, 2 H, CH 2 ), 6.52 (d, J= 9.2 103 Hz, 2 H, Ar-H), 6.56 (d, J= 9.2 Hz, 2 H, Ar-H), 6.85 (d, J= 8.72 Hz, 2 H, Ar-H), 7.20 (d, J 8.72 Hz, 2 H, Ar-H), 7.50 (s, 1 H, Ar-CH=N-), 7.83 (s, 1 H, Imid-H), 9.68 (brs, 1 H, D 2 0 exchangable NH), 1 3 C NMR (100 MHz, d 6 -DMSO): 8 = 40.4 (visible in DEPT 135), 42.8, 55.6, 64.8, 112.4, 114.4, 121.3, 124.4, 127.1, 129.1, 129.4, 134.7, 137.2, 145.9, 150.7, 154.7,155.8, 159.1. HRMS (FAB) Calcd for C23H23NO 2 , 429.1913 (M*); observed m/z 430.1980 (M+H)t. [0588] Synthesis of 1,3,7, 9 b-Tetrahydro-9b-(2,3,4-trimethoxyphenyl)-3-[(4 methoxyphenyl)methylJ-2f-diimidazo[4,5-d:4',5'J-][1,31diazepin-2-one (14): MeO OMe OMe OMe WN

NN

N HN N-/ [05891 To a stirred suspension of 3 (0.43 g, 1 mmol) in 1, 2

,

3 -trimethoxybenzene (5 mL), TFA (10 mL, dropwsie) was added. The reaction mixture was heated at 60 "C for 3 h. TFA was evaporated on rotary evaporator after the disappearance of starting material (TLC) and excess of sodium bicarbonate was added. The reaction mixture was extracted with EtOAc (30 x 3 mL), washed with brine, dried (anhyd. Na 2

SO

4 ) and adsorbed over silica and purified through column chromatography to afford 14 as yellowish white solid (0.38 g, 80%); mp: decomposed > 225 "C. IR: 1734 (C=0 str.), 1620, 1514, 1247 (C-O str.) cm-. 'H NMR (400 MHz, d 6 -DMSO): S = 3.52 (s, 3 H, OCH 3 ), 3.69 (s, 6 H, OCH 3 ), 4.60 (dd, J= 15.1, 18.3 Hz, 2 H, CH 2 ), 5.80 (J= 8.7 Hz, 1 H, Ar-H), 6.50 (J= 8.7 Hz, I H, Ar-H), 6.85 (d, J= 8.7 Hz, 2 H, Ar-H), 7.22 (d, J= 8.7 Hz, 2 H, Ar-H), 7.50 (s, 1 H, Ar-CH=N-), 7:85 (s, I H, Imid-H), 9.40 (brs, I H, D20-exchangable NH).

'

3 C NMR (100 MHz, d 6 -DMSO): S = 42.9, 55.6, 56.3, 60.7, 60.8, 63.4, 106.7, 114.2, 120.0, 122.0, 122.8, 129.1, 129.9, 134.9, 137.2, 142.0, 146.0, 152.6, 154.2, 154.7, 156.6, 159.1. HRMS (FAB) Caled for C24H24N 6 OS, 476.1808 (M*); observed m/z 477.1875 (M+H)t 104 [05901 Reaction of 3 with phenol in TFA: Formation of 1,3,7,9b-Tetrahydro-9b-(o hydroxyphenyl)-3-[(4-methoxyphenyl)methyl]-2H-diimidazof4,5-d.4',5'-] 11,31diazepin-2 one (Ortho Isomer)) and 1,3, 7 ,9b-Tetrahydro-9b-(p-hydroxyphenyl)-3-[(4 methoxyphenyl)methyl]-2H-diimidazo[4,5-d:4',5'-][1,3]diazepin-2-one (Para Isomer): OMe NMe HO OMe

SOH

0 /NN N N N N N+N N N N N N\ TFA, 60 C, 3 h HN N HN N o-isomer p-isomer OMe [0591J To a stirred suspension of 3 (0.43 g, 1 mmol) in phenol (5 mL), TFA (10 mL, dropwsie) was added. The reaction mixture was heated at 60 *C for 3 h. TFA was evaporated on rotary evaporator after the disappearance of starting material (TLC) and excess of sodium bicarbonate was added.. The reaction mixture was extracted with EtOAc (30 x 3 mL), washed with brine, dried (anhyd. Na 2

SO

4 ) afford mixture of o and p isomers (0.37 g, 79%) and were not separated. 105 P , O Oe O e N N N ZU 7

.

7 1134 105921 Reaction of 3 with aniline in TFA: 10593] To a stirred suspension of 3 (0.43 g, I mmol) in aniline (5 mL), TFA (10 mL, dropwsie) was added. The reaction mixture was heated at 60 *C for 2 h. The multiple spots (more than 8) appeared on TLC and were not separated. [0594] Reaction of 3 with nitrobenzene in TFA: [0595] To a stirred suspension of 3 (0.43 g, I mmol) in nitobenzene (5 mL), TFA (10 mL, dropwsie) was added. The reaction mixture was heated at 60 "C for 12 h. The starting material remained unchanged. 105961 Synthesis of Comound 21: An Analogue of Compound 3with an Ortho chlorophenyl Substituent at the 7-Position 106 Cl NN 0

OCH

3 N N N N Compound 21 3, 7 -Dihydro-3-[(4-methoxyphenyl)methyl}-7-[(2-chlorophenyl)methyl]-2H-diimidazo[4,5 d:4',5'-f][1,3}diazepin-2-one Synthetic Scheme 4 -A CI EtO H NH2 CI HNqH <N NH2 21 91 1N N 2 NCN N CI Aniline hydrochloride NC N DBU (Cat.) C

C

1 N + (Cat.) 11 DyEOr,2,N CN NC NH 2 EsBOH, rt 6 h NC NH 2 Dry EtOH, rt, 2h, N 2 HN 515 16 17 Me C OCN 'Dry MeCN, N 2 C OMe

O

0 CO-t, 6 h NN

NH

2 NH <N HC(OEN DBU (Cat.) N NH ~J~/N(Ot 3 MecNrefiux N-f rt, I h N .-N H C h1.5 h, 12SO4 (cat.)N N hN O 0 NC Y 21 20 19 (+20) 10.7 {0597] Synthesis of Compound 23 An analogue of Compound 3 with a 2'-Deoxyribosyl Substituent at the 7-Position MeOw 2 HN 9 N 8 \N4 N HO N 5 OMe HO Compd. 23 1,3, 7

,

9 b-Tetrahydro-9b-(4-methoxyphenyl)-3-[(4-methoxyphenyl)methyl]-7-(2'-deoxy-p-D erythropentofuranosyl)-2H-diimidazo[4,5-d:4',5'-fj[1,3]diazepin-2-one Synthetic Scheme 5 MaO OMe Me O MaO N\ p-TO jO K cI N NN N p-oIO N N MeOH. NaOMe (1 drop) H I N NaH, MeCN, Me t 2-3 h HO YOMe MN NS'rt.,3 h p-TIO'jJaaM~J(~ 11 p-TolO 22 HO 23 (RK-4) [05981 ( 2 -Chlorobenz)-(Z-N-(2-amino-1.2-dicvanovinyj)formimidine (16) [0599] o-Chlorobezylamine (15, 0.77 mL, 6.39 mmol, 1.05 equiv) was added to a suspension of imidate 5 (1 g, 6.09 mmol, I equiv) in dry EtOH which contained aniline hydrochloride (0.02 g). The mixture was stirred at room temperature until TLC (1:1 EtOAc/hexane) showed that all the formimidate had disappeared (-6 h) and the pale yellow solid was obtained by filtration, washed with diethyl ether and dried to give pure 16 (1.2 g, 73%). 'H NMR (400 MHz, d 6 -DMSO): 8 = 4.57 (d, J= 5.9 Hz, 2 H, ClH 2 ), 6.10 (s, 2 H, NH 2 ), 7.29-7.31 (m, 2 H, Ar-H), 7.42-7.44 (m, 2 H, Ar-H), 7.74 (d, J= 3.7 Hz, I H, CH), 8.16 (d, J= 4.6 Hz, I H, NH). [0600] 5-Amino-l-(2-chlorobenzyl)-4-cyanoformimidoylimidazole (17) [0601] To a suspension of 16 (1.0 -g) in dry EtOH (5 mL), DBU was added (1 drop). The reaction mixture was stirred 2 h at room temperature under nitrogen atmosphere until starting 108 material was disappeared (TLC). The precipitated product was filtered, washed with diethyl ether and dried under vacuum to afford the pure product 17 as off-white solid (0.69 g, 69%). IR : 3290 (N-H str.), 2360 (CN str.), 1631 (C=N str.), 1554, 754 (C-Cl str.) cm-'. .H NMR (400 MHz, d, DMSO): 8 = 5.19 (s, 2 H, CH 2 ), 6.74-6.76 (in, I H, Ar-H), 6.82 (brs, 2 H, NH 2 ), 7.24 (s, 1 H, Imid-H), 7.31-7.36 (m, 2 H, Ar-H), 7.51-7.54 (in, I H, Ar-H), 10.97 (s, 1 H, NH). (0602] 4-(1-(2-Chlorobenzyl)-5-amino-1H-imidazol-4-yl)-1-(4-methoxvbenzyl)-5-imino-1H imidazoi-2(5H)-one (20) [0603] To a suspension of 17 (1.0 g, 3.86 mmol, 1 equiv) in dry MeCN (10 mL), 4 methoxybenzyl isocyanate was added (0.94 mL, 5.79 mmol, 1.5 equiv) under nitrogen atmosphere. The reaction mixture was stirred 6 h until starting material was disappeared (TLC). The yellow precipitate was filtered, washed with diethyl ether and dried under vacuum to afford the mixture of 19 and 20 as a yellow solid (1.2 g). Further, 1 drop of DBU was added to a suspension of the mixture in acetonitrile, and the reaction mixture was stirred for 1 h. The deep yellow precipitate was filtered, washed with diethyl ether and dried under vacuum to afford 20 as a yellow solid (0.8 g). IR : 3218 (N-H str.), 1702 (C=O str.), 1649 (C=N, str.), 1598, 1443, 1247 (C-O str.), 753 (C-Cl str.) cm'. 'H NMR (400 MHz, d 6 -DMSO): 6 = 3.71 (s, 3 H, OCH 3 ), 4.64 (s, 2 H, CH 2 ), 5.27 (s, 2 H, CH 2 ), 6.79-6.82 (m, 1 H, Ar-H), 6.86 (d, J= 8.7 Hz, 2 H, Ar-H), 7.23 (d, J= 8.7 Hz, 2 H, Ar-H), 7.31-7.39 (m, 2 H, Ar-H), 7.53-7.55 (in, I H, Ar-H), 7.63 (s, I H, Imid-H), 7.99 (brs, 2 H, NH 2

D

2 0-exchangable), 9.78 (s, 1 H, NH D20-exchangable). 106041 3,7-Dihydro-3-[(4-methxphenyllmethyll-7-l(2-chlorophenyl)methyll-2H diimidazol4.5-d:4',5'-fill.3ldiazeyin-2-one (21) [0605] To a suspension of 20 (3.5 g, 8.29 mmol, 1 equiv) in MeCN (30 mL), triethyl orthoformate (6.2 mL, 41.46 mmol, 5 equiv) was added followed by 4 drops of sulfuric acid. The reaction mixture was heated at reflux for 1.5 h until starting material was disappeared (TLC). The precipitated product was filtered, washed with diethyl ether and dried under vacuum to afford the pure product 21 (RK-12) as a pale yellow solid (3 g, 85%). IR: 1745 (C=0 str.), 1621, 1586, 1248, 1171, 759 (C-Cl str.) em'. 'H NMR (400 MHz, dr-DMSO): 5 = 3.71 (s, 3 H,

OCH

3 ), 5.09 (s, 2 H, CH 2 ), 5.68 (s, 2 H, CH 2 ), 6.86 (d, J= 8.7 Hz, 2 H, Ar-H), 6.98-6.99 (m, I H, Ar-H), 7.25-7.27 (in, 1 H, Ar-H), 7.30 (d, J = 8.7 Hz, 2 H, Ar-H), 7.34-7.38 (in, 1 H, Ar-H), 109 7.53-7.55 (m, 1H, Ar-H), 8.70 (s, 1 H, Ar-C=N-H), 8.86 (s, 1 H, Imid-H). MS (ESI +ve) m/z: 433.2 (M+H), 455.1(M+Na)*. [06061 L.

3

.

7

.

9 b-Tetrahydro-9b-(4-methoxyphenvl)-3-f(4-methoxvphenylmethyll-7-l(2' deoxy- 4 '5'-his(0-p-toluoyl)-p-D-erythropentofuranosvl)1-2H-diimidazol4,5-d:4',5' fIll,3ldiazepin-2-one (22) 106071 To a suspension of 11 (0.2 g, 0.48 mmol, 1 equiv) in dry acetonitrile (10 mL), sodium hydride (60% suspension, 40 mg, 1.2 mmol, 2.5 equiv ) was added and the mixture was stirred at rt under nitrogen atmosphere for 30 min. 2 -Deoxy- 3 ,5-di-0-p-toluoyl-a-D-erythropentofuranosy chloride (186 mg, 0.48 mmol, I equiv) was added portionwise over a period of 30 min. After the addition is complete, the reaction mixture was stirred for 2 h. It has then filtered and evaporated under reduced pressure. The residue was purified by column chromatography on a silica gel to afford a pure off-white solid (0.25 g, 68%). mp: 100-101 "C, 'H NMR (400 MHz, d 6 -DMSO): 8 = 2.37 (s, 3 H, OCH 3 ), 2.42 (s, 3 H, OCH 3 ), 2.72-2.83 (in, 2 H), 3.68 (s, 3 H, OCH 3 ), 3.77 (s, 3 H, OCH 3 ), 4.57-4.71 (m, 5 H, 2 H+3 H), 5.68-5.72-(m, iH), 6.42 (m, 1 H), 6.66-6.84 (m, 5 H), 7.20-7.25 (m, 7 H), 7.66-7.95 (m, 6 H), MS (ESI +ve) m/z: 769 (M+H) 106081 1.

3

.

7

.

9 b-Tetrahydro-9b-(4-methoxhenv).3.4crmethoxphenl)methyll-7-L(2' deoxy-8-D-erythropentofuranosyl)l2H-diimido4, -d:4'.5'-fill,3ldiazepin-2-one (23) 106091 To a solution of 22 (0.25 g) in MeOH (10 mL), sodium methoxide (1 drop) was added at rt. The reaction mixture was stirred for 2-3 h. After the completion of reaction (TLC), reaction mixture was adsorbed over silica gel and purified by column chromatography to afford a pure white solid (100 mg, 58%); mp: 130-132 "C, IR : 1763 (C=O str.), 1621, 1513, 1252.(C-0 str.), 1171 cm'. 'H NMR (400 MHz, d 6 -DMSO): S = 3.40-3.60 (m, 2 H), 3.67 (s, 3 H, OCH 3 ), 3.72 (s, 3 H, OCH1 3 ), 3.78-3.82 (m, 2 H), 4.01-4.05 (m, IH), 4.30-4.33 (m, IH), 4.62 (s, 2 H, CH 2 ), 4.92 4.96 (in, IH, D20-exchangable OH), 5.25-5.28 (in, 114, D20-exchangable OH), 6.20 (m, I H,), 6.68-6.69 (in, 2 H, Ar-li), 6.80-6.81 (in, 2 H, Ar-H), 6.86-6.89 (m, 2 H, Ar-H), 7.19-7.23 (m, 2 H, Ar-H), 7.58 (s, 1 H, Ar-CH=N-), 8.21 (d, J = 8.2 Hz, I H, Imid-H), 9.87 (s, 1 H, D 2 0 exchangable NH), MS (ESI +ve) ni/z: 533 (M+H)*. 110 [06101 Synthesis of Compound 25: An Analogue of RK-33 with a Para-nitrophenyl Substituent at the 5-Position 1 O / ~3a 0

$

NO

2 Compound 25 3,7-Dihydro-3,7-bis[(4-methoxyphenyl)methyl]-5-(4-nitrophenyl)-2H-diimidazo[4,5-d:4',5' f][1,3]diazepin-2-one (25) (AK-104) [06111 Synthesis of 3

,

7 -Dihvdro-3,7-bis[(4-methoxyphenyl)methyll-5-(4-nitrophenvl)-2H diimidazol4,5-d:4',5'-fl1,lldiazeyin-2-one (25) 0 0 N CHO NA N N H 2

SO

4 (cat) N <1 I NH' + DMF, 80 0 C < N -e

NH

2 0 NO 2 0 9 24 25 (AK-104)

NO

2 10612] To a solution of 9 (150 mg, 0.36 mmol, 1.0 equi.) in DMF (1 mL) was added 4 nitrobenzaldehyde (24) (60 mg, 0.395 mmol, 1.1 equi.) and heated at 80"C for 6 h. Reaction mixure was cooled and water was added to form a precipitate. The precipitate was filtered and washed with water. The residue was then dried and recrystalised from 1:1 ethanol and CHC 3 for get the pure compound 25 (80 mg, 40%). H NMR (400 MHz,DMSO-D6): S = 3.65 (s, 6 H, 2 x OCH,), 5.19 (s, 2 H, CH2), 5.62 (s, 2 H, CH 2), 6.86 (dd, J= 8.4 Hz, 12.0 Hz, 2 H, Ar-H), 7.37 (d, J= 8.4 Hz, 13.0 Hz, 2 H, Ar-H), 8.37 (d, J= 8.8 Hz, 2 H, Ar-H), 8.78 (d, J= 8.8 Hz, 2 H, Ar-H),'8.97 (s, I H, lmid-H). MS (ESI) mr/z 550 (M + H)*. 111 [0613] Synthesis of Compound 27: An Analogue of Compound 3 with a 2,4,5 Tricarboxyphenyl Substituent at the 5-Position 0 N J N NN N

HO

2 C

CO

2 H Compound 27 3, 7 -Dihydro-3,7-bis[(4-methoxyphenyl)methyll-5-(2,4,5-tricarboxyphenyl)-2H-diimidazo[4,5 d:4',5'-A[1,3]diazepin-2-one (27) (AK-1 19) [06141 Synthesis of 3,7-Dihydro-3,7-bisl(4-methoxyphenylmethyll-5-(2,4.5 tricarboxyphenyl)-2H-diimidazo4.5-d:4'.5'-f[1 ,3ldiazepin-2-one (27) 9 0 2 (A Nok 0 0 N imN N I N-\H 2 S0g (cat) N <Nf\ \ + oPII1JIIo b </ NHMF.860 0 C NJ-\ V NH/ 0 0 H0 2 C 9 26 27 (AK-1 19) [0615J To a solution of 9 (150 mg, 0.36 mci, 1.0 equl.) in DMF (3 mL) was added 1,2,4,5 benzenetetracaroxylic dianhydride (26) (400 mg, 1.83 mmol, 5.1 equi.) and heated at 80*C for 15 112 h. Reaction mixture was cooled and water was added to form a precipitate. The precipitate was filtered and washed with water to obtain the product 27 (150 mg, 65%). H NMR (400 MHz,DMSO-D6): 6 = 3.66 (s, 6 H, 2 x OCH3), 5.06 (s, 2 H, CH2), 5.48 (s, 2 H, CH 2 ), 6.82 (dd, J 8.4 Hz, 12.0 Hz, 4 H, Ar-H), 7.35 (d, J= 8.4 Hz, 13.0 Hz, 4 H, Ar-H), 7.93 (s, 1 H, Ar-H), 7.94 (s, I H, Ar-H), 8.94 (s, I H, Imid-H). MS (ESI) m/z 637 (M + H) 4 . 6.1.1. Results [0616] Without being limited by theory, it is believed that the compound of the invention down regulate the expression of DDX3, a member of the DEAD box RNA helicase family. [0617] It has now been surprisingly found that the compounds of the invention can kill cancer cells but not affect normal cells at the concentration of the drug used. [0618} The immunoblot analyses were performed to show the DDX3 levels in the respective cell lines. Also it can kill prostate cancer cell line (PC-3) and human glioblastoma cell line (U87). [0619] Purpose: The CellTiter One Solution Assay (Promega) is a colorimetric method for determining the number of viable cells in proliferation or cytotoxicity assays. The One Solution contains MTS compound and an electron coupling reagent PES. The MTS compound is bioreduced by cells into a colored formazan product that is soluble in tissue culture medium. The quantity of formazan product as measured by the amount of 490nm absorbance is directly proportional to the number of living cells in culture. [0620] 1. 25, 000 cells were seeded in 24 well plate in duplicate for each concentration of drug. [0621] 2. 24 hours after seeding, we replaced the medium with drug containing fresh medium. Cells were incubated with drug for 72hrs. After completion of the treatment drug containing media was replaced with MTS reagent. Culture medium "no-cell" control was used as a negative control at the same time. [0622] 3. Absorbance at 490nm (450-540nm) was measured using a plate reader. The absorbance values were subtracted from "no-cell" control, which yield the corrected absorbance. 10623] Results [0624] QRT-PCR of DDX3 levels in a series of immortalized normal breast cell lines (1-2) and breast cancer cell lines (3-7) are illustrated in Figure 1. The breast cancer cell lines are in the order of aggressive phenotype. Immunoblot analysis for DDX3 expression in the identical cell lines as above. QRT-PCR of DDX3 levels in different grades of human breast carcinoma 113 samples. Immunostaining for DDX3 levels in normal human breast sections and in breast carcinoma sample. [0625] Tumor growth rate in the mammary fat pad of SCID mice (preclinical breast cancer model) using wild type and DDX3 knobkdo wn MDA-MB-231 cells is illustrated in Figure 2. Cross section of lungs of animals injected orthotopically (mammary fat pad) with MDA-MB-231 and MDA-MB-23 I -shDDX3 cells. Note that the lungs from MDA-MB-23 1 -shDDX3 injected animals showed no tumor formation as compared to the wild type cells (black arrows points to lung metastasis). [06261 MTS assays of MCF lOA cells (immortalized normal breast cell line) incubated with Compound 3 are illustrated in Figure 3. X-axis indicates concentration of drug used. The cells were incubated for three days (fresh drug was added daily) following which cell viability was determined. [0627] MTS assays of MCF 10A cells (immortalized normal breast cell line) incubated with Compound 3 are illustrated in Figure 4. X-axis indicates concentration of drug used. The cells were incubated for three days (fresh drug was added daily) following which cell viability was determined. [06281 MTS assays of MCF-7 cells (breast cancer cell line) incubated with Compound 3 are illustrated in Figure 5. X-axis indicates concentration of drug used. The cells were incubated for three days (fresh drug was added daily) following which cell viability was determined. 106291 MTS assays of MDA-MB-468 cells (breast cancer cell line) incubated with Compound 3 are illustrated in Figure 6. X-axis indicates concentration of drug used. The cells were incubated for three days (fresh drug was added daily) following which cell viability was determined. [06301 MTS assays of MDA-MB-231 cells (breast cancer cell line) incubated with Compound 3 are illustrated in Figure 7. X-axis indicates concentration of drug used. The cells were incubated for three days (fresh drug was added daily) following which cell viability was determined. [0631] MTS assays of HL60T cells (leukemia cell line) incubated with Compound 3 are illustrated in Figure 8. X-axis indicates concentration of drug used. The cells were incubated for three days (fresh drug was added daily) following which cell viability was determined. [0632J MTS assays of 1NT34 cells (leukemia cell line) incubated with Compound 3 are illustrated in Figure 9. X-axis indicates concentration of drug used. The cells were incubated for three days (fresh drug was added daily) following which cell viability was determined. 114 [06331 MTS assays of KG 101 cells (leukemia cell line) incubated with Compound 3 are illustrated in Figure 10. X-axis indicates concentration of drug used. The cells were incubated for three days (fresh drug was added daily) following which cell viability was determined. 106341 Toxicity studies of Compound 3 were conducted in SCID mouse. Data shown is that of 500 pM of Compound 3 drugs that were injected twice daily for four weeks. Following that the drug was injected once a week for three weeks. At the end of the experiment the animals were sacrificed and histopathology performed. The range of drug dose tested was from 500 to 100 pM. [0635] The results confirm that the illustrative compounds of the invention were successful in killing cancer cell lines while at the same time not affecting normal cells. [0636] The present invention is not to be limited in scope by the specific embodiments disclosed in the examples which are intended as illustrations of a few aspects of the invention and any embodiments which are functionally equivalent are within the scope of this invention. Indeed, various modifications of the invention in addition to those shown and described herein will become apparent to those skilled in the art and are intended to fall within the appended claims. 10637] A number of references have been cited, the entire disclosures of which are incorporated herein by reference. 115

Claims

1. A method of treating a hyperproliferative disorder susceptible to treatment by downregulation of DDX3 comprising administering to a subject in need thereof an effective amount of a composition or formulation comprising a compound of Formula (I). r(R 9 9(b) ' ..--- N N 7N N3 6 N N4 5 (I) or pharmaceutically acceptable salts and prodrugs thereof, wherein: R, R', and R are each independently a hydrogen, hydroxyl; substituted or unsubstituted: cyclic or acyclic alkyl group, cyclic or acyclic alkenyl group, cyclic or acyclic alkynyl group, aryl group, alkylaryl group, arylalkyl group, benzyl group, cyclic and acyclic heteroalkyl group, heteroaryl group; -C(O)R 3 ; -C(S)R 3 ; -S(O)R 3 ; -S(O) 2 R 3 ; -C(O)NR 3 R 4 ; C(S)NR 3 R 4 ; C(S)YR 3 ; -C(O)YR 3 ; -p-D-ribosyl; -a-D-ribosyl; -p-L-ribosyl; -a-L-ribosyl; 2'-deoxy-p-D-ribosyl; 2'-deoxy-p-L-ribosyl; 2'-deoxy-a-D-ribosyl; 2'-deoxy-a-L ribosyl; or ribose or deoxyribose sugars substituted with one or more halogens; R, R', and R can also form a ring with one or more C, S, 0, N atoms such that, for example, R and R' together include: R7 R7 is a hydrogen; hydroxyl; substituted and unsubstituted: cyclic and acyclic alkyl group, group, alkenyl group, alkynyl group, aryl group, aryloxy group, alkylary group, aryalkyl group, heteroaryl group, heterocycloalkyl group; -C(O)alkyl; -C(O)alkenyl; -C(O)atkynyl; 116 -C(O)aryl; -C(O)benzyl; -C(O)NR 3 R 4 ; -C(S)alkyl; -C(S)alkenyl; -C(S)alkynyl; -C(S)aryl; -C(S)benzyl; -C(S)NR 3 R 4 ; -C(O)N R 3 R 4 ; -C(S)YR 3 ; -C(O)YR 3 ; wherein -Q is =0, =NH, or =S; Y is O or S; Z is CH, N, P, or C; --- is a single bond or double bond; wherein if ------ is a double bond, R2 or R7 is independently 0, S, or NH; n is 1, 2, 3, or 4; R3 and R 4 are independently a hydrogen; hydroxyl; substituted or unsubstituted: cyclic or acyclic alkyl group, cyclic or acyclic alkenyl group, cyclic or acyclic alkynyl group, aryl group, alkylary group, aryalkyl group, heteroaryl group, heterocycloalkyl group; and r, r', and r" are each independently an integer from 1 to 3.

2. The method of claim 1, wherein the compound is MeO N N OMe N N N

3. The method of claim I or claim 2, wherein the hyperproliferative disorder is selected from the group consisting of lung cancer, prostate cancer, glioblastoma, or breast cancer.

4. The method of claim 3, wherein the hyperproliferative disorder is prostate cancer or glioblastoma.

5. A method of identifying a subject having a hyperproliferative disorder susceptible to treatment by down regulation of DDX3 comprising: obtaining a cell or tissue sample from tissue of the subject associated with or suspected to be associated with the disorder; measuring expression of DDX3 in the tissue or in the cells isolated from the tissue; and 117 identifying the subject as having the hyperproliferative disorder as susceptible to treatment by down regulation of DDX3 if DDX3 is expressed in the tissue or cell sample.

6. The method of claim 5, wherein the hyperproliferative disorder is selected from the group consisting of lung cancer, prostate cancer; brain cancer including glioblastoma, medulloblastoma, and pontine tumors; or breast cancer.

7. The method of claim 5, wherein the hyperproliferative disorder is prostate cancer or glioblastoma.

8. The method of any one of claims 5-7, wherein measuring comprises immunohistochemistry analysis of the tissue sample.

9. The method of any one of claims 5-7, further comprising isolating cells from the tissue sample and measuring expression of DDX3 in the tissue comprises measuring expression of DDX3 in the cells.

10. The method of claim 9, further comprising performing an assay by exposing the cells to a compound of Formula (I) that downregulates DDX3, measuring cell viability as a function of concentration and identifying the hyperproliferative disorder as susceptible to treatment by down regulation of DDX3 if cell viability decreases as a function of concentration, wherein Formula (I); 9( 9(b)1Q -N NY N R N 6 N4 (I) or pharmaceutically acceptable salts and prodrugs thereof, wherein: 118 R, R', and R are each independently a hydrogen, hydroxyl; substituted or unsubstituted: cyclic or acyclic alkyl group, cyclic or acyclic alkenyl group, cyclic or acyclic alkynyl group, aryl group, alkylaryl group, arylalkyl group, benzyl group, cyclic and acyclic heteroalkyl group, heteroaryl group; -C(O)R 3 ; -C(S)R 3 ; -S(O)R 3 ; -S(O) 2 R 3 ; -C(O)NR 3 R 4 ; C(S)NR 3 R"; -C(S)YR 3 ; -C(O)YR 3 ; -p-D-ribosyl; -a-D-ribosyl; -p-L-ribosyl; -x-L ribosyl; 2'-deoxy-p-D-ribosyl; 2'-deoxy-p-L-ribosyl; 2'-deoxy-c-D-ribosyl; 2'-deoxy-a L-ribosyl; or ribose or deoxyribose sugars substituted with one or more halogens; R, R', and R can also form a ring with one or more C, S, 0, N atoms such that, for example, R and R' together include: R7 (Z)n R7 is a hydrogen; hydroxyl; substituted and unsubstituted: cyclic and acyclic alkyl group, group, alkenyl group, alkynyl group, aryl group, aryloxy group, alkylary group, aryalkyl group, heteroaryl group, heterocycloalkyl group; -C(O)alkyl; -C(O)alkenyl; -C(O)alkynyl; -C(O)aryl; -C(O)benzyl; -C(O)NR 3 R 4 ; -C(S)alkyl; -C(S)alkenyl; -C(S)alkynyl; -C(S)aryl; -C(S)benzyl; -C(S)NR 3 R 4 ; -C(O)N R 3 R 4 ; -C(S)YR 3 ; -C(O)YR 3 ; wherein -Q is =0, =NH, or =S; Y is O or S; Z is CH, N, P, or C; ------ is a single bond or double bond; wherein if ----- is a double bond, R2 or R 7 is independently 0, S, or NH; n is 1, 2, 3, or 4; R3 and R4 are independently a hydrogen; hydroxyl; substituted or unsubstuted: cyclic or acyclic alkyl group, cyclic or acyclic alkenyl group, cyclic or acyclic alkynyl group, aryl group, alkylary group, aryalkyl group, heteroaryl group, heterocycloalkyl group; and r, r', and r" are each independently an integer from 1 to 3. 119

11. The method of claim 10, wherein the assay comprises a MTS assay.

12. The method of claim 10, wherein the compound is MeO OMe rN N N 12 120